Pneumocystis carinii Infection in Transgenic B Cell-Deficient Mice

Abstract

Pneumocystis carinii is an important cause of pneumonia in immunocompromised hosts. Both cellular and humoral immunity seem important in resistance to this pathogen, but the specific role of each component is poorly understood. An outbreak of P. carinii pneumonia in transgenic B cell-deficient mice (muMT) was studied. Over 4 months, >50% of 41 muMT/muMT mice maintained in a sterile environment died of pneumonia. Some mice had concurrent infection with Pasteurella pneumotropica. Homozygous muMT/muMT mice had no detectable serum immunoglobulins, while their heterozygous muMT/+ counterparts had normal levels of IgM, IgG, and IgA and did not develop pneumonia. The infection was controlled by treating the mice with trimethoprim-sulfamethoxazole, and the pathogen was eliminated by cesarean rederivation. These observations suggest an important role for B cells in the host defense against P. carinii.

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

“…In this report, we confirm the findings of others (11,12) that mice deficient in B cells are more susceptible to PCP and are unable to resolve a primary infection. The increased susceptibility of B celldeficient mice could be due to the absence of P. carinii-specific Ab; however, B cells also function as APC (29 -31) and are able to produce a diverse array of cytokines (32,33), indicating that they might play additional roles in the immune response.…”

“…It has been previously reported that mice deficient in B cells (MT mice) are susceptible to PCP (11,12). Furthermore, it is known that CD40L expression on T cells is necessary for resolution of P. carinii infection since individuals with mutations in the CD40L gene (X-linked hyper-IgM syndrome) are susceptible to opportunistic infections including P. carinii, Cryptosporidium, and Candida (22,23).…”

“…Indeed, several groups have now shown that B cell-deficient (MT) mice are highly susceptible to P. carinii infection (11)(12)(13). Although it is not known how B cells contribute to the resolution of P. carinii infection, there have been a number of studies indicating that IgG Abs produced by B cells can mediate clearance of P. carinii (14 -19).…”

CD8 T Cells Modulate CD4 T-Cell and Eosinophil-Mediated Pulmonary Pathology in Pneumocystis Pneumonia in B-Cell-Deficient Mice

“…15 We first compared these two models and found that at 28 days after inoculation MT mice exhibited a burden of Pneumocystis that is only slightly lower than that seen in CD4 ϩ depleted wild-type mice infected at the same time ( Figure 1). However, there were some subtle differences in the Pneumocystis-related pathology found in these two models.…”

“…Because these mice cannot produce functional antibodies, they develop fullblown PCP despite the presence of CD4 lymphocytes. 15 By depletion of specific lymphocyte subsets using antibodymediated depletions, we examined the type and onset of pathology during PCP in MT mice that were deficient in CD4 lymphocytes, CD8 lymphocytes, or both CD4 and CD8 lymphocytes, as well as mice that were replete in both CD4 and CD8 lymphocytes. We report here that significant inflammatory damage occurs in both CD4-depleted and CD8-depleted MT mice during Pneumocystis infection, although it may occur via different mechanisms.…”