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Asthma is a global and increasingly prevalent disease. According to the World Health Organization, approximately 235 million people suffer from asthma. Studies suggest that fine particulate matter (PM2.5) can induce innate immune responses, promote allergic sensitization, and exacerbate asthmatic symptoms and airway hyper-responsiveness. Recently, severe asthma and allergic sensitization have been associated with T-helper cell type 17 (TH17) activation. Few studies have investigated the links between PM2.5 exposure, allergic sensitization, asthma, and TH17 activation. This study aimed to determine whether (1) low-dose extracts of PM2.5 from California (PMCA) or China (PMCH) enhance allergic sensitization in mice following exposure to house dust mite (HDM) allergen; (2) eosinophilic or neutrophilic inflammatory responses result from PM and HDM exposure; and (3) TH17-associated cytokines are increased in the lung following exposure to PM and/or HDM. Ten-week-old male BALB/c mice (n = 6–10/group) were intranasally instilled with phosphate-buffered saline (PBS), PM+PBS, HDM, or PM+HDM, on days 1, 3, and 5 (sensitization experiments), and PBS or HDM on days 12–14 (challenge experiments). Pulmonary function, bronchoalveolar lavage cell differentials, plasma immunoglobulin (Ig) protein levels, and lung tissue pathology, cyto-/chemo-kine proteins, and gene expression were assessed on day 15. Results indicated low-dose PM2.5 extracts can enhance allergic sensitization and TH17-associated responses. Although PMCA+HDM significantly decreased pulmonary function, and significantly increased neutrophils, Igs, and TH17-related protein and gene levels compared with HDM, there were no significant differences between HDM and PMCH+HDM treatments. This may result from greater copper and oxidized organic content in PMCA versus PMCH. [ABSTRACT FROM AUTHOR]

The characterization of host immune responses to human immunodeficiency virus (HIV) in HIV controllers and individuals with high exposure but seronegativity to HIV (HESN) is needed to guide the development of effective preventive and therapeutic vaccine candidates. However, several technical hurdles severely limit the definition of an effective virus-specific T-cell response. By using a toggle-peptide approach, which takes HIV sequence diversity into account, and a novel, boosted cytokine staining/flow cytometry strategy, we here describe new patterns of T-cell responses to HIV that would be missed by standard assays. Importantly, this approach also allows detection of broad and strong virus-specific T-cell responses in HESN individuals that are characterized by a T-helper type 1 cytokine–like effector profile and produce cytokines that have been associated with potential control of HIV infection, including interleukin 10, interleukin 13, and interleukin 22. These results establish a novel approach to improve the current understanding of HIV-specific T-cell immunity and identify cellular immune responses and individual cytokines as potential markers of relative HIV resistance. As such, the findings also help develop similar strategies for more-comprehensive assessments of host immune responses to other human infections and immune-mediated disorders. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate and characterize the therapeutic potential of curdlan, a naturally occurring β-glucan immunomodulator, against visceral leishmaniasis, a fatal parasitic disease. Curdlan eliminated the liver and spleen parasite burden in a 45-day BALB/c mouse model of visceral leishmaniasis at a dosage of 10 mg/kg/day as determined by Giemsa-stained organ impression smears. Curdlan was associated with production of the disease-resolving T-helper (Th) 1 and Th17-inducing cytokines interleukin (IL)-6, IL-1β, and IL-23, as well as with production of Th17 cytokines IL-17 and IL-22, as determined by enzyme-linked immunosorbent assay (ELISA) and real time polymerase chain reaction (RT-PCR). Reversal of curdlan-mediated protection by anti-IL-17 and anti-IL-23 monoclonal antibodies showed the importance of Th17 cytokines. Significantly decreased production of both IL-17 and IL-22 by mice that received anti-IL-23 antibody suggested the essential role of IL-23 in Th17 differentiation. Although administration of recombinant IL-17 or IL-23 caused significant suppression of the organ parasite burden, with marked generation of interferon γ and nitric oxide (NO), effects were much faster for IL-17. These results documented that although both IL-23 and IL-17 play major roles in the antileishmanial effect of curdlan, the effect of IL-23 may occur indirectly, through the induction of IL-17 production. [ABSTRACT FROM AUTHOR]