Sex-Differential Impact of Human Cytomegalovirus Infection on In Vitro Reactivity to Toll-Like Receptor 2, 4 and 7/8 Stimulation in Gambian Infants

Abstract

Human cytomegalovirus (HCMV) infection rates approach 100% by the first year of life in low-income countries. It is not known if this drives changes to innate immunity in early life and thereby altered immune reactivity to infections and vaccines. Given the panoply of sex differences in immunity, it is feasible that any immunological effects of HCMV would differ in males and females. We analysed ex vivo innate cytokine responses to a panel of toll-like receptor (TLR) ligands in 108 nine-month-old Gambian males and females participating in a vaccine trial. We found evidence that HCMV suppressed reactivity to TLR2 and TLR7/8 stimulation in females but not males. This is likely to contribute to sex differences in responses to infections and vaccines in early life and has implications for the development of TLR ligands as vaccine adjuvants. Development of an effective HCMV vaccine would be able to circumvent some of these potentially negative effects of HCMV infection in childhood.

Keywords

• human cytomegalovirus
• human infants
• innate immunity
• sex differences
• vaccination
• toll-like receptor