HIV This Week

Induction of Innate Immune Responses in the Female Genital Tract: Friend or Foe of HIV-1 Infection?

Firoz Mian M, Ashkar AA. Am J Reprod Immunol. 2011 Mar;65(3):344-51

Heterosexual transmission of HIV-1 and HSV-2 across the genital tract epithelial tissue is one of the primary routes for dissemination of these viral infections. Mucosal innate immunity is the first line of defense against invading pathogens. A vast majority of mucosal HIV-1 exposures do not result in productive infections which may indicate that the innate mucosal immune system is highly protective. It has been shown that Toll-like receptors (TLR)-induced innate antiviral immunity in the genital mucosa lead to induction of type I and III interferon and prevention of HSV-2 infection. The innate antiviral function of type I and III interferons and other innate factors at genital mucosa against HIV-1 is not well defined. In this review, Firoz Mian and Ashkar summarize their current understanding and advances of the innate mucosal response to genital viral infections, including HIV-1 and HSV-2, focusing on those factors that may prevent or accelerate initial infection. Understanding how each of these components contributes to mucosal innate antiviral immunity may lead to the development of novel and effective strategies to use microbicides or antiviral agents to control HIV-1 acquisition and/or transmission.

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Editors’ note: Innate immunity is our first line of defence against viruses, limiting their replication until adaptive immunity steps in. However, much of the work to date on immunological responses to HIV has focused on adaptive immunity in the search for an HIV vaccine. It is important to understand whether innate immunity at the mucosal level protects against HIV and, if so, how it works. Immune mechanisms vary by site—this review focuses on the innate immune response in the female genital tract. It includes mechanical interference, immediate cytokine/chemokine and interferon responses to prevent viral replication and spread, and rapid recruitment of cellular defences. Hormones, secreted mediators (e.g. human β-defensins, secretory leukoprotease inhibitors, lactoferin, trappin-2/elafin), toll-like receptors (TLR)—all regulate the immune response in the complex female genital tract microenvironment. For example, toll-like receptors recognise conserved pathogen-associated molecular patterns (PAMPs) made by invading pathogens and link to pathogens, triggering local inflammation, recruitment of effector cells, and secretion of cytokines/chemokines and interferon (IFN). But HIV is wily, inhibiting host defence factors and evading the TLR-IFN pathway to take advantage of inflammatory responses to replicate in the cells that have responded to the call for help. In the search for effective anti-HIV microbicides, we need to take advantage of what we know about innate immunity and learn more.