Affiliation:
1. Department of Immunology
2. Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania 15261
3. Division of Pulmonary, Allergy, and Critical Care Medicine
Abstract
ABSTRACT
Pulmonary colonization by the opportunistic pathogen
Pneumocystis jiroveci
is common in HIV
+
subjects and has been associated with development of chronic obstructive pulmonary disease (COPD). Host and environmental factors associated with colonization susceptibility are undefined. Using a simian-human immunodeficiency virus (SHIV) model of HIV infection, the immunologic parameters associated with natural
Pneumocystis jiroveci
transmission were evaluated. SHIV-infected macaques were exposed to
P. jiroveci
by cohousing with immunosuppressed,
P. jiroveci
-colonized macaques in two independent experiments. Serial plasma and bronchoalveolar lavage (BAL) fluid samples were examined for changes in antibody titers to recombinant
Pneumocystis
-kexin protein (KEX1) and evidence of
Pneumocystis
colonization by nested PCR of BAL fluid. In experiment 1, 10 of 14 monkeys became
Pneumocystis
colonized (Pc
+
) by 8 weeks post-SHIV infection, while 4 animals remained
Pneumocystis
colonization negative (Pc
−
) throughout the study. In experiment 2, 11 of 17 animals became
Pneumocystis
colonized by 16 weeks post-SHIV infection, while 6 monkeys remained Pc
−
. Baseline plasma KEX1-IgG titers were significantly higher in monkeys that remained Pc
−
, compared to Pc
+
monkeys, in experiments 1 (
P
= 0.013) and 2 (
P
= 0.022). Pc
−
monkeys had greater percentages of
Pneumocystis
-specific memory B cells after SHIV infection compared to Pc
+
monkeys (
P
= 0.037). After SHIV infection, Pc
+
monkeys developed progressive obstructive pulmonary disease, whereas Pc
−
monkeys maintained normal lung function throughout the study. These results demonstrate a correlation between the KEX1 humoral response and the prevention of
Pneumocystis
colonization and obstructive lung disease in the SHIV model. In addition, these results indicate that an effective
Pneumocystis
-specific memory B-cell response is maintained despite progressive loss of CD4
+
T cells during SHIV infection.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
35 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献