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Pneumocystis colonization in immunocompetent and simian immunodeficiency virus-infected cynomolgus macaques.

ABSTRACT: Pneumocystis (Pc) colonization is common among human immunodeficiency virus (HIV)-infected subjects, although the clinical consequences of Pc carriage are not fully understood. We examined the frequency of asymptomatic carriage in healthy and simian immunodeficiency virus (SIV)-infected cynomolgus macaques by use of polymerase chain reaction (PCR) and assessment of changes in the serologic response to a recombinant fragment of the Pc protein kexin (KEX1). Anti-KEX1 antibodies were detected in 95% of healthy monkeys. To create a model of natural transmission of Pc, SIV-infected monkeys were cohoused with macaques coinfected with SIV and Pc. Pc colonization occurred when the CD4(+) T cell count decreased to <500 cells/microL, despite anti-Pc prophylaxis with trimethoprim-sulfamethoxazole. Increases in anti-KEX1 antibody titers preceded detection of Pc DNA in bronchoalveolar lavage (BAL) fluid samples by use of PCR. These results demonstrate the usefulness of recombinant KEX1 in serologic studies of Pc colonization and will improve the understanding of Pc transmission and clinical consequences of Pc colonization in HIV-infected patients.

SUBMITTER: Kling HM

PROVIDER: S-EPMC2622722 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Pneumocystis colonization in immunocompetent and simian immunodeficiency virus-infected cynomolgus macaques.

Kling Heather M HM Shipley Timothy W TW Patil Sangita S Morris Alison A Norris Karen A KA

The Journal of infectious diseases 20090101 1

Pneumocystis (Pc) colonization is common among human immunodeficiency virus (HIV)-infected subjects, although the clinical consequences of Pc carriage are not fully understood. We examined the frequency of asymptomatic carriage in healthy and simian immunodeficiency virus (SIV)-infected cynomolgus macaques by use of polymerase chain reaction (PCR) and assessment of changes in the serologic response to a recombinant fragment of the Pc protein kexin (KEX1). Anti-KEX1 antibodies were detected in 95 ...[more]

PMID: 19014344

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Project description:Toll-like receptors (TLRs) are crucial to the innate immune response. They regulate inflammatory reactions by initiating the production of pro-inflammatory cytokines and chemokines. TLRs also play a role in shaping the adaptive immune responses. While this protective response is important for eliminating infectious pathogens, persistent activation of TLRs may result in chronic immune activation, leading to detrimental effects. The role of TLR2 in regulating HIV-1 infection in vivo has yet to be well described. In this study, we used an SIV-infected rhesus macaque model to simulate HIV infection in humans. We evaluated the plasma of the macaques longitudinally and found a significant increase in the soluble TLR2 (sTLR2) level after SIV infection. We also observed an increase in membrane-bound TLR2 (mb-TLR2) in cytotoxic T cells, B cells, and NK cells in PBMC and NK cells in the gut after infection. Our results suggest that sTLR2 regulates the production of various cytokines and chemokines, including IL-18, IL-1RA, IL-15, IL-13, IL-9, TPO, FLT3L, and IL-17F, as well as chemokines, including IP-10, MCP-1, MCP-2, ENA-78, GRO-α, I-TAC, Fractalkine, SDF-1α, and MIP-3α. Interestingly, these cytokines and chemokines were also upregulated after the infection. The positive correlation between SIV copy number and sTLR2 in the plasma indicated the involvement of TLR2 in the regulation of viral replication. These cytokines and chemokines could directly or indirectly regulate viral replication through the TLR2 signaling pathways. When we stimulated PBMC with the TLR2 agonist in vitro, we observed a direct induction of various cytokines and chemokines. Some of these cytokines and chemokines, such as IL-1RA, IL-9, IL-15, GRO-α, and ENA-78, were positively correlated with sTLR2 in vivo, highlighting the direct involvement of TLR2 in the regulation of the production of these factors. Our findings suggest that TLR2 expression may be a target for developing new therapeutic strategies to combat HIV infection.

Dataset Information

Pneumocystis colonization in immunocompetent and simian immunodeficiency virus-infected cynomolgus macaques.

Publications

Pneumocystis colonization in immunocompetent and simian immunodeficiency virus-infected cynomolgus macaques.

Similar Datasets

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