title: Murine Plasmodium chabaudi malaria increases mucosal immune activation and the expression of putative HIV susceptibility markers in the gut and genital mucosae.
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.
authors.affiliation: Departments of *Medicine; †Laboratory Medicine and Pathobiology; ‡Immunology, University of Toronto, Toronto, Ontario, Canada; §Department of Medical Microbiology University of Nairobi, Nairobi, Kenya; and ‖Sandra A. Rotman Laboratories, Sandra Rotman Centre for Global Health, Tropical Disease Unit, Toronto General Hospital, University Health Network.
authors.forename: Duncan
authors.initials: D
authors.lastname: Chege
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Higgins
authors.forename: Chloe R
authors.initials: CR
authors.lastname: McDonald
authors.forename: Kamnoosh
authors.initials: K
authors.lastname: Shahabi
authors.forename: Sanja
authors.initials: S
authors.lastname: Huibner
authors.forename: Taylor
authors.initials: T
authors.lastname: Kain
authors.forename: Dylan
authors.initials: D
authors.lastname: Kain
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Kim
authors.forename: Nelly
authors.initials: N
authors.lastname: Leung
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amin
authors.forename: Kaoru
authors.initials: K
authors.lastname: Geddes
authors.forename: Lena
authors.initials: L
authors.lastname: Serghides
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Philpott
authors.forename: Joshua
authors.initials: J
authors.lastname: Kimani
authors.forename: Scott
authors.initials: S
authors.lastname: Gray-Owen
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Kain
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
mesh_terms: D000818:Animals; D004198:Disease Susceptibility; D005260:Female; D005434:Flow Cytometry; D041981:Gastrointestinal Tract / Q000276:immunology*; D020869:Gene Expression Profiling; D005835:Genitalia / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D018928:Immunity, Mucosal; D008213:Lymphocyte Activation; D008288:Malaria / Q000150:complications / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016788:Plasmodium chabaudi / Q000276:immunology*; D015728:Receptors, HIV / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015728:Receptors, HIV