- Top of page
- How does HIV cross the mucosal barrier?
- Potential innate defenses against HIV in the genital tract
- In vivo innate immune correlates of altered HIV susceptibility
- The adaptive immune system: too little too late?
- The genetics of HIV susceptibility
- Translating natural HIV protection into prevention
- Summary and future directions
Most human immunodeficiency virus (HIV) is acquired during sex, across a mucosal membrane. Despite many advances in our understanding of HIV pathogenesis, the initial events during mucosal transmission have been poorly characterized, and a better understanding of these events will probably be a key to the development of successful microbicide(s) and/or a preventative HIV vaccine. While a vast majority of mucosal HIV exposures do not result in productive infection, implying that innate mucosal immune defenses are highly protective, failure of these mucosal defenses resulted in over 3 million new HIV infections in 2006. We review recent findings regarding HIV mucosal immunopathogenesis, emphasizing the importance of innate immunity in natural protection from infection, and examine how natural or induced perturbations in the mucosal innate system may underpin HIV transmission. Given the great challenges to the development of HIV microbicides and vaccines, identification and enhancement of ‘natural’ innate immune defenses present attractive avenues for development of safe, non-toxic microbicides.