This is illustrated in infection with Chlamydia trachomatis, Salmonella Typhimurium, Francisella Doramapimod cost tularensis, Mycobacterium tuberculosis, and Leishmania major. In the case of Chlamydia infection, B-cell-deficient and FcγR-deficient mice not only have a significantly higher mortality rate than wild-type mice in lethal challenges but also show reduced Th1 responses and fail to mount an efficient DTH response 37–39. Analogous observations have been made when protection against S. Typhimurium was studied. As seen in Chlamydia infection, B-cell-deficient mice are not protected against lethal challenge with Salmonella and develop reduced Th-cell responses marked by lower levels

of IFN-γ and IL-2 40, 41. In addition, when Ab-opsonized Salmonella are added to DCs in vitro, the DCs process and present Ag more efficiently than in the absence of Abs and

are able to stimulate enhanced T-cell activation 42, 43. The interaction of Abs with activating LY2157299 in vitro FcγRs is also required for optimal protection in M. tuberculosis-infected mice, as aerogenically infected μMT mice, as well as FcRγ−/− mice, show exacerbated immunopathology corresponding with elevated pulmonary recruitment of neutrophils and increased levels of IL-10 in the lung 44, 45. On the contrary, mice lacking inhibitory FcγRIIB manifest enhanced mycobacterial control upon infection and have increased Montelukast Sodium levels of Th1-promoting IL-12 45. Similarly, the protective effect of passively transferred Abs against Francisella has been attributed to limited sequelae associated with infection and an increased T-cell response in the presence of Abs 46, 47. Protective

effects of Ab–FcR interactions on T-cell responses have also been described for infections with intracellular parasites as described in the next section. In the absence of specific Abs, L. major amastigotes are phagocytosed by macrophages, which present Ag on MHC class II and activate memory, but not naïve, T cells; however, when L. major-specific IgG is present, amastigotes are taken up by DCs via FcγRI and II, which results in DC activation and production of IL-12 by the DCs. In contrast to macrophages, DCs are able to effectively prime naïve T cells and the resulting Th1 response leads to smaller lesions and reduced parasite burden 48. On the contrary, the presence of Abs during Leishmania mexicana infection drives a Th2 response and leads to the development of chronic lesions, whereas FcRγ−/− mice are resistant and able to resolve lesions by mounting a Th1 response. Resistance to L. mexicana is also observed in FcγRIII−/− mice, indicating that this receptor is responsible for shifting T-cell responses toward a Th2 phenotype via IL-10 production by macrophages 49, 50.