In:
Infection and Immunity, American Society for Microbiology, Vol. 78, No. 10 ( 2010-10), p. 4320-4330
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.
Type of Medium:
Online Resource
ISSN:
0019-9567
,
1098-5522
DOI:
10.1128/IAI.00507-10
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2010
detail.hit.zdb_id:
1483247-1
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