Anti-IL17A Monoclonal antibody

The proinflammatory cytokine interleukin-17A (IL-17A) is known to mediate antimicrobial activity, but its role during rhinovirus (RV) infections and in asthma needs further investigation. Therefore, we addressed the role of IL-17A during allergic asthma and antiviral immune response in human and murine immunocompetent cells. In this studywefound that asthmatic children with a RV infection in their upper airways have upregulated mRNA levels of the antiviral cytokine interferon type I (IFN)-beta and the transcription factor T-box 21 (TBX21) and reduced levels of IL-17A protein in their peripheral blood mononuclear cells (PBMCs). We also found that IL-17A inhibited RV1b replication in infected human lung epithelial cells A549. Furthermore, by using gene array analysis we discovered that targeted deletion of Il17a in murine lung CD4(+) Tcells impaired Oas1g mRNA downstream of Ifn beta, independently from RV infection. Additionally, in PBMCs of children with a RV infection in their nasalpharyngeal fluid OAS1 gene expression was found downregulated. Finally RV1b inhibited IL-17A production in lung CD4(+) Tcells in a setting of experimental asthma. These results indicate that the RV1b inhibits IL-17A in T helper type 17 cells and IL-17A clears RV1b infection in epithelial cells. In both cases IL-17A contributes to fend off RV1b infection by inducing genes downstream of interferon type I pathway.

Background: Prior Influenza A viral (IAV) infection has been shown to increase susceptibility to tuberculosis (TB) and TB has also been shown to be a primary cause of death during pandemics, including the Spanish Influenza outbreak of 1918-1919. The majority of data has been obtained from mouse models, thus the aim of this study was to determine the impact of Flu co-infection on host immunity and disease severity in TB patients at diagnosis. Methods: Sputum from 282 patients with active TB were analyzed for presence of FluA/FluB RNA at presentation using multiplex PCR. Sputum RNA was also analyzed for Mycobacterium tuberculosis (Mtb) load using S-16 RNA amplification. Supernatants from digested sputum and Mtb antigen-stimulated whole blood were analyzed using multiplex cytokine arrays and PBMC were analyzed for cytokine production from CD4+ T, CD8+ T and Mucosal Associated Invariant T cells (MAITs). Results: 12 (4.3%) of TB patients were found to have FluA or FluB viral RNA present in their sputum at the time of TB diagnosis. The TB/Flu co-infected patients had a significantly higher bacterial load compared to those with TB mono-infection (p = 0.0026). They had lower levels of IL17A in ex vivo sputum (p = 0.0275) and higher MCP-1 (CCL2) levels in the blood following PPD stimulation (p = 0.0267). TB/Flu co-infected subjects had significantly higher IFN-gamma+IL-17+CD4+ and IFN-gamma+IL-17-CD8+ cells compared to TB mono-infected subjects. Conclusions: These data show that Flu co-infection at time of TB diagnosis is associated with a higher bacterial load and differential cellular and soluble profiles. These findings show for the first time the impact of TB/Flu co-infection in a human cohort and support the potential benefit of Flu vaccination in TB-endemic settings.