TGF-β-Responsive Myeloid Cells Suppress Type 2 Immunity and Emphysematous Pathology after Hookworm Infection

Transforming growth factor beta (TGF-beta) regulates inflammation, immunosuppression, and wound-healing cascades, but it remains unclear whether any of these functions involve regulation of myeloid cell function. The present study demonstrates that selective deletion of TGF-beta RII expression in myeloid phagocytes i) impairs macrophage-mediated suppressor activity, increases baseline mRNA expression of proinflammatory chemokines/cytokines in the lung, and ill) enhances type 2 immunity against the hookworm parasite Nippostrongylus brasiliensis. Strikingly, TGF-beta-responsive myeloid cells promote repair of hookworm-damaged lung tissue, because LysM(Cre)TGF-beta RIIflox/flox mice develop emphysema more rapidly than wild-type littermate controls. Emphysematous pathology in LysM(Cre)TGF-beta RIIflox/flox mice is characterized by excessive matrix metalloprotease (MMP) activity, reduced lung elasticity, increased total lung capacity, and dysregulated respiration. Thus, TGF-beta effects on myeloid cells suppress helminth immunity as a consequence of restoring lung function after infection. (Am J Pathol 2012, 181:897-906 http://dx.doi.org/10.1016/j.ajpath.2012.05.032)