Relationship of Pneumocystis jiroveci humoral immunity to prevention of colonization and chronic obstructive pulmonary disease in a primate model of HIV infection.
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.
Kling
Heather M
HM
Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Shipley
Timothy W
TW
Patil
Sangita P
SP
Kristoff
Jan
J
Bryan
Marianne
M
Montelaro
Ronald C
RC
Morris
Alison
A
Norris
Karen A
KA
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D056724:Immunity, Humoral; D008252:Macaca fascicularis; D045363:Pneumocystis carinii / Q000276:immunology*; D011020:Pneumonia, Pneumocystis / Q000150:complications / Q000382:microbiology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000382:microbiology / Q000517:prevention & control*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications / Q000382:microbiology