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Background: T helper (Th)17 and regulatory T (Treg) cells with toll-like receptor (TLR)-2 have been acknowledged to play a critical role in chronic rhinosinusitis with nasal polyposis (CRSwNP). However, its pathogenesis has been perplexed by conflicting reports on the role of Th17/Treg cells in patients of distinct ethnicities. We attempted to understand the role of Th responses induced during host defense against Aspergillus flavus., Results: The percentages of Th17 (CD4 + CD161 + IL23R + ) and Treg (CD4 + CD25 + FoxP3 + ) cell populations and various cytokine profiles in peripheral blood mononuclear cells (PBMCs) challenged by A. flavus antigens were characterized from 50 CRSwNP cases, before and after treatment, and in 50 healthy controls. TLR-2 expression was analyzed in tissues of cases and controls for disease co-relation. The major pathogen identified in our study was A. flavus by mycological investigations. A marked immune imbalance was noted with elevated Th17 and decreased Tregs in PBMCs of CRSwNP patients after A. flavus stimulation. Comparatively, interleukin (IL)-17 and IL-10 levels were increased, with low transforming growth factor (TGF)-β levels in A. flavus stimulated PBMC supernatants of patients. The mRNA expression of TLR-2 in polyps of CRSwNP patients indicated significant (p = 0.001) upregulation in comparison to the controls., Conclusions: Our data highlights the excessive expression of TLR-2 in nasal polyps contributing to the imbalance in Th17/Tregs population in patients. After therapy, recovery of Tregs cells indicates restoration and tissue homeostasis, though high circulating CD4 + CD161 + Th17 cells may continue to be a threat to patients predisposed to future recurrences. The constant exposure and tendency of A. flavus to colonize nasal cavities can lead to a Th17 driven airway inflammation. Dysregulated Th17 with TLR-2 promote resistance to treatment and progression to the chronicity of the disease.

Background: Fungi, especially Aspergillus flavus, can cause chronic rhinosinusitis with nasal polyposis and modulate host innate immune components. The objective of this study was to examine the serum levels of T helper (Th) cell subset Th1, Th2, and Th17 cytokines and total IgE in patients having chronic rhinosinusitis with nasal polyposis and Aspergillus flavus infection., Methods: A case-control study including 40 patients with chronic rhinosinusitis with nasal polyposis and 20 healthy controls was conducted. Aspergillus flavus infection was confirmed by standard potassium hydroxide (KOH) testing, culture, and PCR. Serum samples of all patients and controls were analyzed for various cytokines (interleukins [IL]-1β, IL-2, IL-4, IL-6, IL-17, IL-21, IL-27, TGF-β) and total IgE by ELISA. Data from patients with Aspergillus flavus infection and healthy volunteers were compared using the independent t-test and non-parametric Mann-Whitney U test., Results: Aspergillus flavus infection was found in 31 (77.5%) patients with chronic rhinosinusitis with nasal polyposis. IL-1β, IL-17, IL-21, and TGF-β serum levels were significantly higher in these patients than in controls; however, IL-2, IL-4, IL-6, and IL-27 levels were lower. Compared with nine (22.5%) patients without Aspergillus flavus infection, IL-17 level was higher while IL-2 level was lower in patients with Aspergillus flavus infection. Total IgE was significantly higher in patients with Aspergillus flavus infection than in controls., Conclusions: High levels of IL-17 and its regulatory cytokines in patients with chronic rhinosinusitis with nasal polyposis infected by Aspergillus flavus raise a concern about effective disease management and therapeutic recovery. Surgical removal of the nasal polyp being the chief management option, the choice of post-operative drugs may differ in eosinophilic vs. non-eosinophilic nasal polyposis. The prognosis is likely poor, warranting extended care., Competing Interests: The authors declare no conflict of interest., (© The Korean Society for Laboratory Medicine)

Pityriasis Versicolor is a skin condition caused by the commensal yeast Malassezia. Little is known about the pathogenesis of why a commensal only causes symptoms in a subset of infected individuals. Understanding the susceptibility of the host to these commensal-associated diseases may be facilitated by knowledge of genetic polymorphism. The purpose was to investigate the relationship between Single Nucleotide Polymorphism in the IL10 and IFN genes of the host and susceptibility to Malassezia infection. There were 38 cases of Pityriasis Versicolor (PV) and 38 healthy controls in the sample. Blood samples were extracted for genomic DNA from all study participants. Amplification refractory mutations system-polymerase chain reaction (ARMS-PCR) with sequence-specific primers was used to genotype cytokines. In all patients and healthy controls, three SNPs (IL10-1082A/G; IL10-819/592C/T; IFN-+874A/T) in two cytokine loci were analyzed. In the PV group, we observed significant differences in allele or genotype distribution for the IL10-819/592C/T and IFN-+874A/T gene polymorphisms. In the present investigation, cytokine gene polymorphism revealed that the host was susceptible to Malassezia infection. [ABSTRACT FROM AUTHOR]

The list of environmental factors that trigger autoimmune diseases in genetically susceptible individuals has grown in the recent years and is far from complete. The possible intervention of the environment in triggering these diseases is ever more perceived by the clinicians. This study investigated the effect of environmental factors like organochlorine pesticides (OCPs) on proportions of different T lymphocyte subsets and their cytokine secretion in-vitro among pemphigus patients, before and after specific immunosuppressive therapy. Higher levels of OCPs like β-HCH (isoform of hexachlorohexane), α-endosulfan (a form of endosulfan) and p,p΄-DDE (a metabolite of o,p'-dichlorodiphenyltrichloroethane) were observed in the blood of pemphigus patients as compared to healthy controls. HCH and DDT exposure caused specific reduction in CD8+CD45RA+ and CD4+CD25+ T lymphocyte subpopulations in these patient PBMCs. A strong reduction in Th1 (IL-2 and IFN-γ) cytokines upon exposure to these OCPs in-vitro was also observed. These findings indicate that HCH and DDT have a significant impact on Th1 lymphocytes. Impaired production of these cytokines might favor infections and production of autoantibodies. We therefore speculate that the systemic absorption of the pesticide after the topical contact may be one of the factors triggering the immunological mechanism among pemphigus patients. • Higher levels of β-HCH, α-endosulfan and p,p΄-DDE found in pemphigus blood. • HCH and DDT reduced CD8+CD45RA+ and CD4+CD25+ T cells in pemphigus PBMCs. • Decreased IL-2 and IFN-γ cytokine release upon in-vitro HCH and DDT exposure. • HCH and DDT have a significant impact on Th1 lymphocytes. • Impaired production of IL-2 and IFN-γ might favor infections and autoantibodies. [ABSTRACT FROM AUTHOR]

Pemphigus is an autoimmune blistering disorder of skin and/or mucosal surfaces characterized by intraepithelial lesions and immunoglobulin-G autoantibodies against desmogleins (proteins critical in cell-to-cell adhesion). Genetic, immunological, hormonal, and environmental factors are known to contribute to its etiology. Tumor necrosis factor-alpha (TNF-α) which plays a key role in pathogenesis of many infectious and inflammatory diseases has been found in high levels in lesional skin and sera of pemphigus patients. However, studies on association of single nucleotide polymorphism (SNP) in promoter region of TNF-α at position −308 affecting G to A transition with pemphigus has been scarce. This study was conducted to evaluate the TNF-α −308G/A SNP distribution in North Indian cohort, and to define the association between the TNF-α −308G/A SNP distribution and pemphigus, globally, by means of meta-analysis. TNF-α −308G/A SNP in pemphigus patients was investigated by cytokine genotyping using genomic DNA by PCR with sequence-specific primers. Meta-analysis of the data, including four previously published studies from other populations, was performed to generate a meaningful relationship. The results of our case–control study indicate non-significant differences between patients and controls in TNF-α −308G/A SNP. The meta-analysis also revealed that TNF-α −308G/A SNP is not associated with pemphigus risk in population at large; however, it may be contributing towards autoimmune phenomenon in pemphigus by being a part of its multi-factorial etiology. This study provides evidence that the TNF-α −308G/A polymorphism is not associated with overall pemphigus susceptibility. Nevertheless, further studies on specific ethnicity and pemphigus variants are necessary to validate the findings. [ABSTRACT FROM AUTHOR]

Abstract Background Human Cytomegalovirus (CMV), because of its ability to extensively manipulate host immunity during active infection, has been suggested to be involved in autoimmunity. However, its influence on T-cells and cytokines in systemic autoimmune diseases like systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is indistinct. Methods We investigated the in-vitro response of T lymphocytes from SLE and SSc patients to CMV antigen. Functional activity of T lymphocytes was determined by estimating Th1 (IL-2 and IFN-γ) and Th2 (IL-4 and IL-10) cytokines. Results We observed that CMV antigen stimulation in-vitro resulted in significant increase in CD4:CD8 T-cell ratio in peripheral blood mononuclear cells (PBMCs) from SLE and SSc patients; response dominated by CD4+ than CD8+ memory T-cells. SSc T-cell response was differentiated by aberrant increase in CD4+CD25+ T-cells. CMV antigen caused elevation in IL-4 and IFN-γ production in both patient PBMCs, whereas IL-2 was also raised in SLE PBMCs. The development of large pool of memory T-cells and overproduction of IFN-γ may result in flare-up of autoimmunity in these patients. Conclusion Our study provides an insight into the immunopathological potential of CMV-reactive immune cells to develop new potential strategies for targeted therapeutic intervention. Highlights • Elevation in CD4:CD8 T cell ratio in SLE and SSc patient PBMC on CMV stimulation. • Aberrant increase in percentages of CD4+CD25+ T cells differentiates SSc from SLE. • IFN-γ overproduction and large memory T cell pool may lead to IL-2 release. • Abating naıve T cell pool, particularly of CD4 repertoire, flares up autoimmunity. [ABSTRACT FROM AUTHOR]

Interleukin-17 producing T helper (Th17) and regulatory T cells (Treg) cells have been identified to play a critical role in atopic inflammation. However, conflicting reports on the role of Th17/Treg cells in allergic fungal rhinosinusitis (AFRS) patients of different ethnicities has mystified its pathogenesis. To better understand the pathophysiological mechanisms involved in AFRS, we conducted a prospective, analytical, case-control study involving 40 confirmed immunocompetent AFRS patients and 20 healthy controls. The distribution of Th17 and Treg cells in PBMC, intracellular mRNA expression of retinoid orphan nuclear receptor (RORγt) in Th17 and forkhead transcription factor (FoxP3) in Treg cells, and serum cytokine levels were investigated. Aspergillus flavus was identified from majority (85%) of patient tissue biopsies. Total serum IgE level along with cytokines IL-17, IL-21, IL-1β and TGF-β were comparatively elevated in AFRS. Nevertheless, IL-2 and IL-10 were reduced. Higher percentages of CD3 + CD4 + T cells in AFRS with increased expression of CD161 and/or IL-23R markers were observed. Though, lower percentages of CD4 + CD25 + Treg cells with elevated expression of GITR were patent. Transcription factor RORγt mRNA was upregulated, whereas FoxP3 mRNA was downregulated in AFRS patients. This inclination of Th17/Treg balance towards Th17, and the proposed role of Tregs on Th1 and Th2 cells in AFRS, directed us to conclude that Aspergillus infestation may lead to development of atopy and immunological dysbalance inciting a Th17 driven response, thereby, promoting aggravation of nasal polyposis. The observation may provide new insight into the molecular mechanisms leading to revision of the classical paradigm. [ABSTRACT FROM AUTHOR]

Elevated inflammation is a known risk factor in the pathogenesis of PTB. Despite intensive research, the etiology of idiopathic PTB is still unknown. The present study was designed to explore associations of blood concentrations of organochlorine pesticides (OCPs) with inflammatory/antioxidant gene expression, and cytokines and prostaglandin levels in PTB cases. Significantly high levels of α, β-hexachlorocyclohexane (α, β-HCH), dichlorodiphenyldichloroethane ( o’p’- DDD), dichlorodiphenyldichloroethylene ( p’p’ -DDE), increased expression of cyclooxygenase-2 (COX-2), and decreased expression of manganese superoxide dismutase (Mn-SOD) and catalase (CAT) genes were seen in PTB cases. Also, increased protein levels of interleukin-6 (IL-6) and decreased protein levels of interleukin-4 (IL-4) and prostaglandin F2α (PGF2α) were found in maternal blood of PTB cases as compared to term controls. Elevated levels of β-HCH along with high expression of COX-2 gene or low expression of Mn-SOD or CAT genes were associated with the decrease in the period of gestation (POG). [ABSTRACT FROM AUTHOR]

The delineation of the pathogenic interaction between the host skin immune responses and dermatophytes has remained indigent. The obscure enigma in host-dermatophyte immunopathogenic interactions is the T regulatory (Treg) and T-helper (Th) 17 cell role in maintaining immune homeostasis. We attempted to understand the regulation and recognition of lineage-specific response in chronic dermatophytic skin infection patients. The percentages of Th17 (CD4+CD161+IL23R+) and Treg (CD4+CD25+FoxP3+) cell subpopulations in the peripheral circulation of thirty chronic dermatophytic skin infection patients and twenty healthy individuals was determined. The serum cytokine levels were estimated for disease correlation. The mean duration of the disease was 10.68 ± 8.72 months, with Trichophyton mentagrophytes complex as the major pathogen. Total serum IgE level of patients was significantly higher compared to healthy controls (305 ± 117 vs 98.53 ± 54.55 IU/ml; p < 0.01). Expression of Th17 and Treg cell markers on CD4+ T cells was significantly elevated in patients than controls (p < 0.05). Comparatively, serum interleukin (IL)-4 and interferon (IFN)-γ levels were increased, with low IL-10 levels in patients. Our data envisages a complex immune dysfunction in chronic dermatophytosis, arising either as a result of dermatophyte exposure or paradoxical precedence of disease establishment. Designing new treatment strategies and preventing recurrences are challenges for future research. • Th17 and Treg expression was elevated in dermatophytosis patients than controls. • Patient serum levels of IL-4 and IFN-γ were increased with decreased IL-10 levels. • A complex immune dysfunction was observed in patients of chronic dermatophytosis. [ABSTRACT FROM AUTHOR]