Clearance ofPneumocystis cariniiin Mice Is Dependent on B Cells But Not onP. carinii-Specific Antibody

Abstract

Both CD4+ T cells and B cells are critical for defense against Pneumocystis carinii infection; however, the mechanism by which B cells mediate protection is unknown. We show that P. carinii-specific IgM is not sufficient to mediate clearance of P. carinii from the lungs since CD40-deficient mice produced normal levels of specific IgM, but were unable to clear the organisms. Using chimeric mice in which the B cells were deficient in CD40 (CD40KO chimeras) we found that clearance of P. carinii infection is delayed compared with wild-type controls. These CD40KO chimeric mice produced normal levels of P. carinii-specific IgM, but did not produce class-switched IgG or IgA. Similarly, clearance of P. carinii was delayed in mice deficient in FcγRI and III (FcγRKO), indicating that P. carinii-specific IgG partially mediates opsonization and clearance of P. carinii. Opsonization of organisms by complement did not compensate for the lack of specific IgG or FcγR, since C3-deficient and C3-depleted FcγRKO mice were still able to clear P. carinii. Finally, μMT and CD40KO chimeric mice had reduced numbers of activated CD4+ T cells in the lungs and lymph nodes compared with wild-type mice, suggesting that B cells are important for activation of T cells in response to P. carinii. Together these data indicate that P. carinii-specific IgG plays an important, but not critical, role in defense against P. carinii. Moreover, these data suggest that B cells also mediate host defense against P. carinii by facilitating CD4+ T cell activation or expansion.

Mechanisms of clearance of nontypeable Haemophilus influenzae from cigarette smoke-exposed mouse lungs

“…The evidence suggests that B-cells may be important cells for the induction of inflammation following pulmonary infection with P. carinii [37]. The data presented here do not support a role for B-cells as a contributory mechanism to exacerbated inflammation, since the inflammatory profile observed in Bcell-deficient mice was similar to that in WT control animals.…”

“…This implies that the cigarette smoke-induced antibodies are instead natural antibodies against conserved bacterial targets, as have been shown to protect against nasal colonisation with H. influenzae in mice [36]. Similarly, LUND et al [37] demonstrated that mice are protected from Pneumocystis carinii in a B-cell and antibody-dependent, but antigen-specific antibody-independent, manner. It should be noted that accumulation of IgA in the airway lumen required a lower threshold of cigarette smoke exposure (once daily) than the threshold necessary for recruitment of neutrophils into the lung lumen (twice daily).…”

Decreased inflammatory response in Toll-like receptor 2 knockout mice is associated with exacerbated Pneumocystis pneumonia

“…Several surface molecules on alveolar macrophages have been shown to interact with Pneumocystis, including Fc-gamma receptor, [5] complement receptor, [6] scavenger receptor, [7] mannose receptor, [8] and dectin-1. [9] TLR2 is a pattern recognition receptor recognizing a large variety of ligands such as peptidoglycan, lipoprotein, lipopeptide, and zymosan.…”

B Cell Production of Tumor Necrosis Factor in Response to Pneumocystis murina Infection in Mice

“…Many studies have demonstrated that both CD4 ϩ T cells and B cells contribute to protection against Pneumocystis infections (3)(4)(5)(6)(7)(8)(9)(10), but the interactive roles of these lymphocytes in host defense have not been fully defined. Previous studies from our laboratory and others have shown that reconstitution of SCID mice with primed wild-type (WT) CD4 ϩ T cells was sufficient to facilitate Pneumocystis murina (the species found in mice) clearance from their lungs (5,6,8).…”