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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0000000000000056
Basic and Translational Science

Murine Plasmodium chabaudi Malaria Increases Mucosal Immune Activation and the Expression of Putative HIV Susceptibility Markers in the Gut and Genital Mucosae

Chege, Duncan PhD*; Higgins, Sarah J. BSc, MSc; McDonald, Chloe R. BSc, MSc*; Shahabi, Kamnoosh BSc*; Huibner, Sanja BSc*; Kain, Taylor BSc*; Kain, Dylan BSc; Kim, Connie J. BSc, MSc*; Leung, Nelly BSc, PhD; Amin, Mohsen BSc, PhD; Geddes, Kaoru BSc, MSc, PhD; Serghides, Lena BSc, PhD; Philpott, Dana J. BSc, PhD; Kimani, Joshua MBCHB, MPH§; Gray-Owen, Scott BSc, PhD; Kain, Kevin C. MD*,†,‖; Kaul, Rupert MD, PhD*,‡,§

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Abstract

Objective: To evaluate if systemic murine malarial infection enhances HIV susceptibility through parasite-induced mucosal immune alterations at sites of HIV sexual exposure.

Background: Malaria and HIV have a high degree of geographical overlap and interact substantially within coinfected individuals. We used a murine model to test the hypothesis that malaria might also enhance HIV susceptibility at mucosal sites of HIV sexual exposure.

Methods: Female C57/BL6 mice were infected with Plasmodium chabaudi malaria using a standardized protocol. Blood, gastrointestinal tissues, upper and lower genital tract tissues, and iliac lymph nodes were sampled 10 days postinfection, and the expression of putative HIV susceptibility and immune activation markers on T cells was assessed by flow cytometry.

Results: P. chabaudi malaria increased expression of mucosal homing integrin α4β7 on blood CD4+ and CD8+ T cells, and these α4β7+ T cells had significantly increased co-expression of both CCR5 and CD38. In addition, malaria increased expression of the HIV co-receptor CCR5 on CD4+ T cells from the genital tract and gut mucosa as well as mucosal T-cell expression of the immune activation markers CD38, Major Histocompatibility Complex -II (MHC-II) and CD69.

Conclusions: Systemic murine malarial infection induced substantial upregulation of the mucosal homing integrin α4β7 in blood as well as gut and genital mucosal T-cell immune activation and HIV co-receptor expression. Human studies are required to confirm these murine findings and to examine whether malarial infection enhances the sexual acquisition of HIV.

© 2014 by Lippincott Williams & Wilkins

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