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

作者：Chege Duncan^*; Higgins Sarah J; McDonald Chloe R; Shahabi Kamnoosh; Huibner Sanja; Kain Taylor; Kain Dylan; Kim Connie J; Leung Nelly; Amin Mohsen; Geddes Kaoru; Serghides Lena; Philpott Dana J; Kimani Joshua; Gray Owen Scott; Kain Kevin C; Kaul Rupert

来源：JAIDS: Journal of Acquired Immune Deficiency Syndromes , 2014, 65(5): 517-525.

DOI：10.1097/qai.0000000000000056

• malaria
• HIV
• susceptibility
• immune activation
• mucosal
• genital
• gut
• alpha 4 beta 7
• CCR5
• CD69
• CD38
• MHC-II

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 alpha 4b beta 7 on blood CD4+ and CD8+ T cells, and these alpha 4 beta 7(+) 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 alpha 4 beta 7 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.