Anti-IL22 polyclonal antibody [Biotin]

Chronic entericMycobacterium aviumssp.paratuberculosis(MAP) infections are endemic in ruminants globally resulting in significant production losses. The mucosal immune responses occurring at the site of infection, specifically in Peyer's patches (PP), are not well-understood. The ruminant small intestine possesses two functionally distinct PPs. Discrete PPs function as mucosal immune induction sites and a single continuous PP, in the terminal small intestine, functions as a primary lymphoid tissue for B cell repertoire diversification. We investigated whether MAP infection of discrete vs. continuous PPs resulted in the induction of significantly different pathogen-specific immune responses and persistence of MAP infection. Surgically isolated intestinal segments in neonatal calves were used to target MAP infection to individual PPs. At 12 months post-infection, MAP persisted in continuous PP (n= 4), but was significantly reduced (p= 0.046) in discrete PP (n= 5). RNA-seq analysis revealed control of MAP infection in discrete PP was associated with extensive transcriptomic changes (1,707 differentially expressed genes) but MAP persistent in continuous PP elicited few host responses (4 differentially expressed genes). Cytokine gene expression in tissue and MAP-specific recall responses by mucosal immune cells isolated from PP, lamina propria and mesenteric lymph node revealed interleukin (IL)22andIL27as unique correlates of protection associated with decreased MAP infection in discrete PP. This study provides the first description of mucosal immune responses occurring in bovine discrete jejunal PPs and reveals that a significant reduction in MAP infection is associated with specific cytokine responses. Conversely, MAP infection persists in the continuous ileal PP with minimal perturbation of host immune responses. These data reveal a marked dichotomy in host-MAP interactions within the two functionally distinct PPs of the small intestine and identifies mucosal immune responses associated with the control of a mycobacterial infection in the natural host.

Th17 cells contribute to mucosal immunity by stimulating epithelial cells to induce antimicrobial peptides, granulopoiesis, neutrophil recruitment, and tissue repair. Recent studies have identified important roles for commensal microbiota and Ahr ligands in stabilizing Th17 gene expression in vivo, linking environmental cues to CD4 T cell polarization. Epigenetic changes that occur during the transition from naive to effector Th17 cells increase the accessibility of il17a, il17f, and il22 loci to transcription factors. In addition, Th17 cells maintain the potential for expressing T-bet, Foxp3, or GATA-binding protein-3, explaining their plastic nature under various cytokine microenvironments. Although CD4 T cells are major sources of IL-17 and IL-22, innate cell populations, including gamma delta T cells, NK cells, and lymphoid tissue-inducer cells, are early sources of these cytokines during IL-23-driven responses. Epithelial cells and fibroblasts are important cellular targets for IL-17 in vivo; however, recent data suggest that macrophages and B cells are also stimulated directly by IL-17. Thus, Th17 cells interact with multiple populations to facilitate protection against intracellular and extracellular pathogens. J. Leukoc. Biol. 90: 263-270; 2011.