title: Sex bias in susceptibility to MCMV infection: implication of TLR9.
abstract: Toll-like receptor (TLR)-dependent pathways control the activation of various immune cells and the production of cytokines and chemokines that are important in innate immune control of viruses, including mouse cytomegalovirus (MCMV). Here we report that upon MCMV infection wild-type and TLR7(-/-) male mice were more resistant than their female counterparts, while TLR9(-/-) male and female mice showed similar susceptibility. Interestingly, 36 h upon MCMV infection TLR9 mRNA expression was higher in male than in female mouse spleens. MCMV infection led to stronger reduction of marginal zone (MZ) B cells, and higher infiltration of plasmacytoid dendritic cells and neutrophils in wild-type male than female mice, while no such sex differences were observed in TLR9(-/-) mice. In accordance, the serum levels of KC and MIP-2, major neutrophil chemoattractants, were higher in wild-type, but not in TLR9(-/-), male versus female mice. Wild-type MCMV-infected female mice showed more severe liver inflammation, necrosis and steatosis compared to infected male mice. Our data demonstrate sex differences in susceptibility to MCMV infection, accompanied by a lower activation of the innate immune system in female mice, and can be attributed, at least in a certain degree, to the lower expression of TLR9 in female than male mice.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université UM 2, Marseille, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Traub
authors.forename: Olivier
authors.initials: O
authors.lastname: Demaria
authors.forename: Lionel
authors.initials: L
authors.lastname: Chasson
authors.forename: Fabienne
authors.initials: F
authors.lastname: Serra
authors.forename: Benoit
authors.initials: B
authors.lastname: Desnues
authors.forename: Lena
authors.initials: L
authors.lastname: Alexopoulou
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D003586:Cytomegalovirus Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D004198:Disease Susceptibility; D005260:Female; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D008099:Liver / Q000473:pathology / Q000821:virology; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000821:virology; D012333:RNA, Messenger / Q000096:biosynthesis; D012737:Sex Factors; D013154:Spleen / Q000473:pathology / Q000821:virology; D051199:Toll-Like Receptor 7 / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000172:deficiency / Q000235:genetics* / Q000276:immunology
chemical_list: D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C477038:Tlr7 protein, mouse; C495370:Tlr9 protein, mouse; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9