| First Author | Kovach MA | Year | 2017 |
| Journal | Mucosal Immunol | Volume | 10 |
| Issue | 5 | Pages | 1320-1334 |
| PubMed ID | 28176791 | Mgi Jnum | J:296074 |
| Mgi Id | MGI:6467016 | Doi | 10.1038/mi.2016.130 |
| Citation | Kovach MA, et al. (2017) IL-36gamma is a crucial proximal component of protective type-1-mediated lung mucosal immunity in Gram-positive and -negative bacterial pneumonia. Mucosal Immunol 10(5):1320-1334 |
| abstractText | Interleukin-36gamma (IL-36gamma) is a member of novel IL-1-like proinflammatory cytokine family that are highly expressed in epithelial tissues and several myeloid-derived cell types. Little is known about the role of the IL-36 family in mucosal immunity, including lung anti-bacterial responses. We used murine models of IL-36gamma deficiency to assess the contribution of IL-36gamma in the lung during experimental pneumonia. Induction of IL-36gamma was observed in the lung in response to Streptococcus pneumoniae (Sp) infection, and mature IL-36gamma protein was secreted primarily in microparticles. IL-36gamma-deficient mice challenged with Sp demonstrated increased mortality, decreased lung bacterial clearance and increased bacterial dissemination, in association with reduced local expression of type-1 cytokines, and impaired lung macrophage M1 polarization. IL-36gamma directly stimulated type-1 cytokine induction from dendritic cells in vitro in a MyD88-dependent manner. Similar protective effects of IL-36gamma were observed in a Gram-negative pneumonia model (Klebsiella pneumoniae). Intrapulmonary delivery of IL-36gamma-containing microparticles reconstituted immunity in IL-36gamma(-/-) mice. Enhanced expression of IL-36gamma was also observed in plasma and bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome because of pneumonia. These studies indicate that IL-36gamma assumes a vital proximal role in the lung innate mucosal immunity during bacterial pneumonia by driving protective type-1 responses and classical macrophage activation. |
