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Urogenital schistosomiasis remains a major global challenge. Optimal management of this infection depends upon imaging-based assessment of sequelae. Although established imaging modalities such as ultrasonography, plain radiography, magnetic resonance imaging (MRI), narrow band imaging, and computerized tomography (CT) have been used to determine tissue involvement by urogenital schistosomiasis, newer refinements in associated technologies may lead to improvements in patient care. Moreover, application of investigational imaging methods such as confocal laser endomicroscopy and two-photon microscopy in animal models of urogenital schistosomiasis are likely to contribute to our understanding of this infection's pathogenesis. This review discusses prior use of imaging in patients with urogenital schistosomiasis and experimentally infected animals, the advantages and limitations of these modalities, the latest radiologic developments relevant to this infection, and a proposed future diagnostic standard of care for management of afflicted patients.

Urogenital schistosomiasis remains a major global challenge. Optimal management of this infection depends upon imaging-based assessment of sequelae. Although established imaging modalities such as ultrasonography, plain radiography, magnetic resonance imaging (MRI), narrow band imaging, and computerized tomography (CT) have been used to determine tissue involvement by urogenital schistosomiasis, newer refinements in associated technologies may lead to improvements in patient care. Moreover, application of investigational imaging methods such as confocal laser endomicroscopy and two-photon microscopy in animal models of urogenital schistosomiasis are likely to contribute to our understanding of this infection's pathogenesis. This review discusses prior use of imaging in patients with urogenital schistosomiasis and experimentally infected animals, the advantages and limitations of these modalities, the latest radiologic developments relevant to this infection, and a proposed future diagnostic standard of care for management of afflicted patients.

IL-4 is crucial in many helminth infections, but its role in urogenital schistosomiasis, infection withSchistosoma haematobiumworms, remains poorly understood due to a historical lack of animal models. The bladder pathology of urogenital schistosomiasis is caused by immune responses to eggs deposited in the bladder wall. A range of pathology occurs, including urothelial hyperplasia and cancer, but associated mechanisms and links to IL-4 are largely unknown. We modeled urogenital schistosomiasis by injecting the bladder walls of IL-4 receptor-alpha knockout(Il4ra−/−) and wild type mice withS. haematobiumeggs. Readouts included bladder histology andex vivoassessments of urothelial proliferation, cell cycle and ploidy status. We also quantified the effects of exogenous IL-4 on urothelial cell proliferationin vitro, including cell cycle status and phosphorylation patterns of major downstream regulators in the IL-4 signaling pathway. There was a significant decrease in the intensity of granulomatous responses to bladder-wall injectedS. haematobiumeggs inIl4ra−/−versus wild type mice.S. haematobiumegg injection triggered significant urothelial proliferation, including evidence of urothelial hyperdiploidy and cell cycle skewing in wild type but notIl4ra−/−mice. Urothelial exposure to IL-4in vitroled to cell cycle polarization and increased phosphorylation of AKT. Our results show IL-4 signaling is required for key pathogenic features of urogenital schistosomiasis, and that particular aspects of this signaling pathway may exert these effects directly on the urothelium. These findings point to potential mechanisms by which urogenital schistosomiasis promotes bladder carcinogenesis.

Urogenital schistosomiasis, Schistosoma haematobium worm infection, afflicts millions of people with egg-triggered, fibrotic bladder granulomata. Despite the significant global impact of urogenital schistosomiasis, the mechanisms of bladder granulomogenesis and fibrosis are ill defined due to the prior lack of tractable animal models. We combined a mouse model of urogenital schistosomiasis with macrophage-depleting liposomal clodronate (LC) to define how macrophages mediate bladder granulomogenesis and fibrosis. Mice were injected with eggs purified from infected hamsters or vehicle prepared from uninfected hamster tissues (xenoantigen and injection trauma control). Empty liposomes were controls for LC: 1) LC treatment resulted in fewer bladder egg granuloma-infiltrating macrophages, eosinophils, and T and B cells, lower bladder and serum levels of eotaxin, and higher bladder concentrations of IL-1α and chemokines (in a time-dependent fashion), confirming that macrophages orchestrate leukocyte infiltration of the egg-exposed bladder; 2) macrophage-depleted mice exhibited greater weight loss and bladder hemorrhage postegg injection; 3) early LC treatment postegg injection resulted in profound decreases in bladder fibrosis, suggesting differing roles for macrophages in fibrosis over time; and 4) LC treatment also led to egg dose-dependent mortality, indicating that macrophages prevent death from urogenital schistosomiasis. Thus, macrophages are a potential therapeutic target for preventing or treating the bladder sequelae of urogenital schistosomiasis.—Fu, C.-L., Odegaard, J. I., Hsieh, M. H. Macrophages are required for host survival in experimental urogenital schistosomiasis.

Urogenital schistosomiasis, infection with Schistosoma haematobium, is linked to increased risk for the development of bladder cancer, but the importance of various mechanisms responsible for this association remains unclear, in part, owing to lack of sufficient and appropriate animal models. New advances in the study of this parasite, bladder regenerative processes, and human schistosomal bladder cancers may shed new light on the complex biological processes that connect S. haematobium infection to bladder carcinogenesis.

Allergen-specific immunotherapy (IT) has been used for the treatment of atopic diseases since the turn of this century. The precise working mechanisms, however, remain to be clarified. The aim of this study was to investigate the role of particular subsets of allergen-specific T cells in the non-atopic individuals, untreated asthmatic children and the asthmatic children receiving immunotherapy. We collected peripheral blood from 16 untreated asthmatic children and 17 asthmatic children receiving immunotherapy over one and half years. All the patients were sensitive to mite allergen. Peripheral blood mononuclear cells (PBMC) were isolated and, in vitro, stimulated with crude mite extract to enrich the mite-specific T-cell population. After 14 days, the enriched mite-specific T cells were stimulated with phorbol-12-myristate-13-acetate (PMA) and ionomycin for intracellular detection of cytokines such as IFN-γ, IL-4 in CD4 + and CD8 + T lymphocytes. The data here demonstrated that the levels of mite-specific IgG4 and IgA increased significantly in asthmatic children after immunotherapy. In addition, both IL-4 expressing CD4 + and CD8 + cells were significantly lower in asthmatic children after immunotherapy compared with those of before treatment and the normal control (p < 0.05). In contrast, the frequency of IFN-γ expressing CD4 + and CD8 + T cells did not significantly differ between untreated and SIT-treated groups. All these data suggested that decreased Type 2 CD4 + and CD8 + T cells might be closely correlated with the regulatory mechanisms of immunotherapy.

Introduction: The cellular microenvironment plays a key role in the pathogenesis of B-cell malignancies (Amé-Thomas, Blood 2007; Podar, Leukemia 2009). Bone marrow stromal cell interactions can provide survival signals to CLL cells (Kurtova, Blood 2009), and stromal cell gene signatures and markers can predict survival outcomes and add prognostic value, respectively, for patients with DLBCL (Lenz, NEJM 2008; Meyer, Am J Clin Pathol 2011). Ibrutinib (ibr), a first-in-class, oral, once-daily inhibitor of Bruton’s tyrosine kinase, has demonstrated single-agent activity in R/R DLBCL (Wilson, Nat Med 2015). In this study, we established an in vitro coculture system and report the effects of stromal cells on ABC-DLBCL cells and their sensitivity to ibr. Methods: The effect of ibr on cell growth was evaluated by luminescent cell viability assay. Flow cytometry was used to evaluate the effect of ibr on cell death in different cell populations. Live-cell imaging detected drug effects on apoptosis at different time points. Gene expression levels in B lymphoma cells were examined by quantitative PCR and NanoString panels. Human cytokines/chemokines were quantified using MILLIPLEX® MAP Kit. Results: Reduced ibr sensitivity was observed in TMD8 DLBCL cells cocultured with HS-5 bone marrow-derived stromal cells. HS-5 cells protected TMD8 cells from ibr-induced apoptosis. Treatment with ibr induced TNFSF10 expression only in TMD8 cells without HS-5 coculture, providing a survival mechanism for escape of ibr-induced cell death. In addition, coculturing with HS-5 decreased surface expression of CD20 but not CD19. Several cytokines/chemokines showed differential expression in the coculture system (increased CCL22 and IL-10; decreased CCL4 and TNFβ). Reduced expression of BCR signaling-related miR-155 was observed in ABC-DLBCL and CLL cell lines with HS-5 coculture, suggesting downregulation of BCR signaling in these cells. The adhesion molecule, SELL, showed decreased expression in the ABC-DLBCL cells cultured with HS-5 as well as in ibr-resistant TMD8 cells, consistent with our observation that ABC-DLBCL patients with poor responses (PD+SD) to ibr have lower SELL expression in their tumor samples. We further assessed expression levels of amino acid metabolism-related genes and demonstrated significant increases of ASS1 and TDO2 in the TMD8 cells cocultured with HS-5. Expression levels of amino acid metabolism-related genes varied across patients with different responses to ibr, further suggesting the importance of amino acid levels in the tumor microenvironment and ibr response. Conclusions: The changes in ABC-DLBCL cells cocultured with stromal cells identified here may provide new insights into cellular cross-talk in the microenvironment. Further investigation into cell-cell interactions and ibr may help stratify patient populations and provide new therapeutic strategies. Citation Format: Hsu-Ping Kuo, Sidney Hsieh, Mint Sirisawad, Chun-Te Chen, Leo W. Cheung, Karl J. Schweighofer, Chia-Lin Hsu, Chi-Ling Fu, Jing Liu, Shiquan Wu, Karl Eckert, Hugh Wang, Mutiah Apatira, Kamaldeep Dhami, Kevin Kwei, Jeff Hsu, Betty Y. Chang. Interaction of B lymphoma cells with the microenvironment affects ibrutinib sensitivity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4197. doi:10.1158/1538-7445.AM2017-4197

Helminth infections affect 1 billion people worldwide and render these individuals susceptible to bacterial coinfection through incompletely understood mechanisms. This includes urinary tract coinfection by bacteria and Schistosoma haematobium worms, the etiologic agent of urogenital schistosomiasis. To study the mechanisms of S. haematobium -bacterial urinary tract coinfections, we combined the first tractable model of urogenital schistosomiasis with an established mouse model of bacterial urinary tract infection (UTI). A single bladder exposure to S. haematobium eggs triggers interleukin-4 (IL-4) production and makes BALB/c mice susceptible to bacterial UTI when they are otherwise resistant. Ablation of IL-4 receptor alpha (IL-4Rα) signaling restored the baseline resistance of BALB/c mice to bacterial UTI despite prior exposure to S. haematobium eggs. Interestingly, numbers of NKT cells were decreased in coexposed versus bacterially monoinfected bladders. Given that schistosome-induced, non-natural killer T (NKT) cell leukocyte infiltration may dilute NKT cell numbers in the bladders of coexposed mice without exerting a specific functional effect on these cells, we next examined NKT cell biology on a per-cell basis. Invariant NKT (iNKT) cells from coexposed mice expressed less gamma interferon (IFN-γ) per cell than did those from mice with UTI alone. Moreover, coexposure resulted in lower CD1d expression in bladder antigen-presenting cells (APC) than did bacterial UTI alone in an IL-4Rα-dependent fashion. Finally, coexposed mice were protected from prolonged bacterial infection by administration of α-galactosylceramide, an iNKT cell agonist. Our findings point to a previously unappreciated role for helminth-induced IL-4 in impairment of iNKT cell-mediated clearance of bacterial coexposure.

Interleukin-12 (IL-12) is a key cytokine, which promotes T helper type 1 (Th1) cell-mediated immunity and inhibits Th2-type responses. It has been previously shown that IL-12 administration during active immunization following a single allergen exposure can prevent antigen-induced increases in immunoglobulin E (IgE) formation, Th2 cytokine production and bronchoalveolar lavage (BAL) eosinophils in a murine model of allergic airway inflammation. Thus, these studies have now been extended and two IL-12 treatment protocols on this murine model were evaluated. Administration of IL-12 during the active immunization strikingly increased Der p I-specific serum IgG2a and transiently decreased the levels of IgG1 and IgE antibodies following multiple allergen challenges. Such early treatment of IL-12 down-regulated IL-5 production and modestly up-regulated interferon-gamma production but did not effect BAL eosinophilia. These results suggest that repeated exposure to antigen and IL-12 is necessary to maintain a persistent Th1-recall response. Furthermore, administration of IL-12 to actively immunized mice, in which Th2-associated responses were established, had a significant effect on IgG2a synthesis and a modest effect on IgE levels, also down-regulation of IL-5 production, and markedly increased interferon-gamma production and abolished recruitment of eosinophils. Therefore, these data indicate that IL-12 can inhibit antigen-induced eosinophil infiltration into airways, despite the existence of a Th2-associated response. Taken together, these studies suggest that IL-12 may be useful as an immunotherapeutic agent in the treatment of such pulmonary allergic disorders as bronchial asthma.

Urogenital schistosomiasis, chronic infection by Schistosoma haematobium, affects 112 million people worldwide. S. haematobium worm oviposition in the bladder wall leads to granulomatous inflammation, fibrosis, and egg expulsion into the urine. Despite the global impact of urogenital schistosomiasis, basic understanding of the associated pathologic mechanisms has been incomplete due to the lack of suitable animal models. We leveraged our recently developed mouse model of urogenital schistosomiasis to perform the first-ever profiling of the early molecular events that occur in the bladder in response to the introduction of S. haematobium eggs. Microarray analysis of bladders revealed rapid, differential transcription of large numbers of genes, peaking three weeks post-egg administration. Many differentially transcribed genes were related to the canonical Type 2 anti-schistosomal immune response, as reflected by the development of egg-based bladder granulomata. Numerous collagen and metalloproteinase genes were differentially transcribed over time, revealing complex remodeling and fibrosis of the bladder that was confirmed by Masson's Trichrome staining. Multiple genes implicated in carcinogenesis pathways, including vascular endothelial growth factor-, oncogene-, and mammary tumor-related genes, were differentially transcribed in egg-injected bladders. Surprisingly, junctional adhesion molecule, claudin and uroplakin genes, key components for maintaining the urothelial barrier, were globally suppressed after bladder exposure to eggs. This occurred in the setting of urothelial hyperplasia and egg shedding in urine. Thus, S. haematobium egg expulsion is associated with intricate modulation of the urothelial barrier on the cellular and molecular level. Taken together, our findings have important implications for understanding host-parasite interactions and carcinogenesis in urogenital schistosomiasis, and may provide clues for novel therapeutic strategies., Author Summary Parasitic Schistosoma haematobium worms cause urogenital schistosomiasis in 112 million people worldwide. These worms lay eggs in the bladder wall, resulting in inflammation, fibrosis (internal scarring), bladder cancer, and passage of eggs into the urine. Indeed, the International Agency for Research on Cancer within the World Health Organization has classified S. haematobium as a “Class I” agent (“Carcinogenic to humans”). Moreover, S. haematobium-induced fibrosis and resulting obstructive kidney failure leads to 150,000 deaths annually. As a result, S. haematobium infection is one of the most important causes of worm-related death globally. In spite of this, research on this parasite is sparse due to a lack of suitable animal models. We have used our recently developed mouse model of urogenital schistosomiasis to understand the global bladder gene response to this infection. Large numbers of genes featured differential transcription after experimental infection, including specific immune response-, fibrosis-, cancer-, and bladder function-related genes. The relevance of these gene-based findings was verified through microscopic examination of egg-exposed bladders. Our data will improve our comprehension of urogenital schistosomiasis, and may help identify new targets for diagnosis and treatment of this disease, and possibly bladder cancer and bladder-based inflammatory disorders as well.

Schistosoma haematobiumis the etiologic agent for urogenital schistosomiasis, a major source of morbidity and mortality for more than 112 million people worldwide. Infection with S. haematobium results in a variety of immunopathologic sequelae caused by parasite oviposition within the urinary tract, which drives inflammation, hematuria, fibrosis, bladder dysfunction, and increased susceptibility to urothelial carcinoma. Since most of the pathology in schistosomasis is directly attributable to the host reaction to eggs and egg-associated antigens, their isolation and study are important experimental techniques. S. haematobium eggs can be collected from infected tissues for injection into other animals or preparation of crude egg extracts. This protocol describes a simple way to isolate eggs. Schistosomes are a biohazard. Workers should wear latex gloves at all times when handling schistosomal materials or any tissues from infected animals.

Mouse bladder wall injection is a useful technique to orthotopically study bladder phenomena, including stem cell, smooth muscle, and cancer biology. Before starting injections, the surgical area must be cleaned with soap and water and antiseptic solution. Surgical equipment must be sterilized before use and between each animal. Each mouse is placed under inhaled isoflurane anesthesia (2-5% for induction, 1-3% for maintenance) and its bladder exposed by making a midline abdominal incision with scissors. If the bladder is full, it is partially decompressed by gentle squeezing between two fingers. The cell suspension of interest is intramurally injected into the wall of the bladder dome using a 29 or 30 gauge needle and 1 cc or smaller syringe. The wound is then closed using wound clips and the mouse allowed to recover on a warming pad. Bladder wall injection is a delicate microsurgical technique that can be mastered with practice.

Background Allergic asthma strongly correlates with airway inflammation caused by cytokines secreted by allergen-specific type-2 T helper (Th2) cells, but the immunologic regulation of cell function is yet to be acquired. Further, IL-10 has been found to exert both antiinflammatory and immunoregulatory activities. This study aimed to elucidate the therapeutic effects of IL-10 administration via adenovirus-mediated gene delivery on airway inflammation in the ovalbumin (OVA)-induced murine model of asthma. Methods BALB/c mice were sensitized by intraperitoneal injections with OVA and challenged by nebulized OVA. The sensitized mice were given an intratracheal delivery of adenoviral vector expressing the murine IL-10 gene (AdIL-10), or mock adenoviral vector 4 days before the inhalation challenge of the OVA. Inflammatory parameters, such as the development of airway hyper-responsiveness (AHR), bronchial lavage fluid eosinophils, and chemokines were assayed. Results Intratracheal administration of AdIL-10 could efficiently inhibit antigen-induced AHR and significantly decrease the number of eosinophils and neutrophils in the bronchoalveolar lavage fluid of OVA-sensitized and challenged mice during the effector phase. Conclusions Our data showed that the intratracheal transfer of the IL-10 gene could affect the recruitment of inflammatory cells during the challenge phase in a way that would result in the inhibition of airway inflammation. These findings suggest that the development of an immunoregulatory strategy based on IL-10 might shed light on more effective treatment. Copyright © 2006 John Wiley & Sons, Ltd.

BackgroundAn increasing prevalence of allergic diseases, such as atopic dermatitis, allergic rhinitis and bronchial asthma, has been noted worldwide. Allergic asthma strongly correlates with airway inflammation caused by the unregulated production of cytokines secreted by allergen-specific type-2 T helper (Th2) cells. This study aims to explore the therapeutic effect of the airway gene transfer of IL-12, IL-10 and TGF-β on airway inflammation in a mouse model of allergic asthma.MethodsBALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injections with OVA and challenged by nebulized OVA. Different cytokine gene plasmids or non-coding vector plasmids were instilled daily into the trachea up to one day before the inhalatory OVA challenge phase.ResultsIntratracheal administration of IL-10, IL-12 or TGF-β can efficiently inhibit antigen-induced airway hyper-responsiveness and is able to largely significantly lower the number of eosinophils and neutrophils in bronchoalveolar lavage fluid of ovalbumin (OVA) sensitized and challenged mice during the effector phase. Furthermore, the effect of IL-10 plasmids is more remarkable than any other cytokine gene plasmid. On the other hand, local administration of IL-4 gene plasmids before antigen challenge can induce severe airway hyper-responsiveness (AHR) and airway eosinophilia.ConclusionOur data demonstrated that anti- inflammatory cytokines, particularly IL-10, have the therapeutic potential for the alleviation of airway inflammation in murine model of asthma.

Allergen-specific immunotherapy (IT) has been used for the treatment of atopic diseases since the turn of this century. The precise working mechanisms, however, remain to be clarified. The aim of this study was to investigate the role of particular subsets of allergen-specific T cells in the non-atopic individuals, untreated asthmatic children and the asthmatic children receiving immunotherapy. We collected peripheral blood from 16 untreated asthmatic children and 17 asthmatic children receiving immunotherapy over one and half years. All the patients were sensitive to mite allergen. Peripheral blood mononuclear cells (PBMC) were isolated and, in vitro, stimulated with crude mite extract to enrich the mite-specific T-cell population. After 14 days, the enriched mite-specific T cells were stimulated with phorbol-12-myristate-13-acetate (PMA) and ionomycin for intracellular detection of cytokines such as IFN-gamma, IL-4 in CD4+ and CD8+ T lymphocytes. The data here demonstrated that the levels of mite-specific IgG4 and IgA increased significantly in asthmatic children after immunotherapy. In addition, both IL-4 expressing CD4+ and CD8+ T cells were significantly lower in asthmatic children after immunotherapy compared with those of before treatment and the normal control (p0.05). In contrast, the frequency of IFN-gamma expressing CD4+ and CD8+ T cells did not significantly differ between untreated and SIT-treated groups. All these data suggested that decreased Type 2 CD4+ and CD8+ T cells might be closely correlated with the regulatory mechanisms of immunotherapy.

Schistosoma haematobium is the etiologic agent for urogenital schistosomiasis, a major source of morbidity and mortality for more than 112 million people worldwide. Infection with S. haematobium results in a variety of immunopathologic sequelae caused by parasite oviposition within the urinary tract, which drives inflammation, hematuria, fibrosis, bladder dysfunction, and increased susceptibility to urothelial carcinoma. While humans readily develop urogenital schistosomiasis, the lack of an experimentally-tractable model has greatly impaired our understanding of the mechanisms that underlie this important disease. We have developed an improved mouse model of S. haematobium urinary tract infection that recapitulates several aspects of human urogenital schistosomiasis. Following microinjection of purified S. haematobium eggs into the bladder wall, mice consistently develop macrophage-rich granulomata that persist for at least 3 months and pass eggs in their urine. Importantly, egg-injected mice also develop urinary tract fibrosis, bladder dysfunction, and various urothelial changes morphologically reminiscent of human urogenital schistosomiasis. As expected, S. haematobium egg-induced immune responses in the immediate microenvironment, draining lymph nodes, and systemic circulation are associated with a Type 2-dominant inflammatory response, characterized by high levels of interleukin-4, eosinophils, and IgE. Taken together, our novel mouse model may help facilitate a better understanding of the unique pathophysiological mechanisms of epithelial dysfunction, tissue fibrosis, and oncogenesis associated with urogenital schistosomiasis., Author Summary Urogenital schistosomiasis (infection with parasitic Schistosoma haematobium worms, the most common human-specific Schistosoma species globally) affects over 112 million people worldwide. S. haematobium worms primarily lay eggs in the bladder, upper urinary and genital tracts, and the host immune response to these eggs is considered to cause almost all associated disease in these organs. Resulting conditions include hematuria (bloody urine), urinary frequency, fibrosis (internal scarring) of the urinary tract, increased risk of bladder cancer, and enhanced susceptibility to contracting HIV. Approximately 150,000 people die annually from S. haematobium-induced obstructive kidney failure alone, making this species one of the deadliest worms worldwide. Despite the importance of S. haematobium, a lack of an experimentally manipulable model has contributed to the paucity of research focusing on this parasite. We have circumvented the barriers to natural S. haematobium oviposition in the mouse bladder by directly microinjecting parasite eggs into the bladder wall. This triggers inflammation, hematuria, urinary frequency, fibrosis, egg shedding, and epithelial changes that are similar to that seen in clinical S. haematobium infections. Our model may provide new opportunities to better understand the basic molecular and cellular immunology of urogenital schistosomiasis and thereby contribute to the development of new diagnostics and therapeutics.

Chronic inflammatory diseases often result in tissue fibrosis through poorly understand mechanisms. Over 112 million people worldwide are infected with the parasitic worm Schistosoma haematobium. Long-term infection with S. haematobium is associated with parasite egg-induced bladder inflammation and bladder fibrosis. Studying S. haematobium infection may provide clues regarding mechanisms of tissue fibrosis in general. We sought to develop and characterize a more reliable mouse model of S. haematobium infection to study inflammatory mechanisms of tissue fibrosis. BALB/c mice underwent bladder wall injection with S. haematobium eggs and exhibited synchronous bladder granuloma development by 4 days post-injection. Egg-injected bladders began showing fibrosis by 14 days post-injection. Urine was serially sampled to profile the proteome by mass spectrometry and revealed that distinct blood, coagulation, and immune proteins were increased in the urine of egg-injected mice relative to controls. Bladder granulomas grew over time and contained many eosinophils and macrophages. Serum cytokines were analyzed by Luminex analysis and showed early and extended upregulation of IL5, IL1A, and VEGF; and late upregulation of multiple chemokines (KC, MCP1, MCP3, and IP10). We have successfully recapitulated inflammation-associated schistosomal bladder fibrosis in mice. We are now poised to employ genetically modified mice to dissect the inflammatory mechanisms which drive bladder fibrosis.