XXXX and M2a alveolar macrophages promote lung defense against the atypical fungal pathogen @entity19141 murina.

@entity26051 @entity19640 @entity23233 @entity19 @entity13128 @entity5003 @entity281 @entity19141 @entity15064 @entity16564 @entity26507 @entity72495 @entity58 @entity669 @entity1312
We have recently reported that @entity19 deficient in the myeloid @entity19640 -family @entity669 kinases @entity26507 , @entity72495 , and @entity16564 ( @entity19640 triple knockout [TKO]) had augmented innate lung clearance of @entity19141 murina that correlated with a higher ability of alveolar macrophages (AMs) from these @entity19 to kill P. murina. In this article, we show that despite possessing enhanced killing, AMs from naive @entity19640 TKO @entity19 did not demonstrate enhanced inflammatory responses to P. murina. We subsequently discovered that both AMs and lungs from P. murina-infected @entity19640 TKO @entity19 expressed significantly greater levels of the M2a markers RELM-a and @entity23233 , and the M2a-associated chemokines @entity15064 and @entity13128 than did wild-type @entity19 . @entity58 and @entity1312 , the primary cytokines that promote M2a polarization, were not differentially produced in the lungs between wild-type and @entity19640 TKO @entity19 . P. @entity281 in @entity19640 TKO @entity19 resulted in enhanced lung production of the novel @entity5003 family cytokine @entity26051 . Immunohistochemical analysis of @entity26051 in lung tissue revealed localization predominantly in the nucleus of alveolar epithelial cells. We further demonstrate that experimental polarization of naive AMs to M2a resulted in more efficient killing of P. murina compared with untreated AMs, which was further enhanced by the addition of @entity26051 . Administration of @entity26051 to C57BL/6 @entity19 increased lung RELM-a and @entity15064 levels, and enhanced clearance of P. murina, despite having no effect on the cellular composition of the lungs. Collectively, these results indicate that M2a AMs are potent effector cells against P. murina. Furthermore, enhancing M2a polarization may be an adjunctive therapy for the treatment of @entity19141 .
