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

Heather M Kling1, Timothy W Shipley, Sangita Patil

  • 1Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.

Insights

Pneumocystis (Pc) colonization is common in human immunodeficiency virus (HIV)-infected individuals. This study used a macaque model to show that increased anti-KEX1 antibodies can precede Pc detection, aiding understanding of HIV-related Pc infections.

Area of Science:

  • Immunology
  • Microbiology
  • Virology

Background:

  • Pneumocystis (Pc) colonization is frequent in human immunodeficiency virus (HIV)-infected individuals, but its clinical impact remains unclear.
  • Understanding Pc transmission and carriage is crucial for managing opportunistic infections in immunocompromised populations.

Purpose of the Study:

  • To investigate the frequency of asymptomatic Pneumocystis colonization in healthy and simian immunodeficiency virus (SIV)-infected macaques.
  • To develop a model for studying natural Pc transmission and its serologic markers in an SIV-macaque model.
  • To evaluate the utility of recombinant Pneumocystis protein kexin (KEX1) in serologic detection of Pc colonization.

Main Methods:

  • Polymerase chain reaction (PCR) was used to detect Pc DNA.
  • Serologic responses to a recombinant fragment of the Pc protein KEX1 were assessed.
  • SIV-infected macaques were cohoused with SIV/Pc-coinfected macaques to model natural Pc transmission.
  • CD4(+) T cell counts were monitored.

Main Results:

  • Anti-KEX1 antibodies were detected in 95% of healthy macaques.
  • Pc colonization occurred in SIV-infected macaques when CD4(+) T cell counts dropped below 500 cells/microL, even with trimethoprim-sulfamethoxazole prophylaxis.
  • Increases in anti-KEX1 antibody titers preceded the detection of Pc DNA in bronchoalveolar lavage (BAL) fluid via PCR.

Conclusions:

  • Recombinant KEX1 is a useful tool for serologic studies of Pneumocystis colonization.
  • This macaque model advances the understanding of Pc transmission dynamics.
  • Findings contribute to understanding the clinical consequences of Pc colonization in HIV-infected patients.

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