Sex differences in HIV-1-mediated immunopathology

Abstract

Purpose of review: The article reviews our current knowledge regarding the role of sex and sex hormones in regulating innate immune responses to viral infections, which may account for the described sex differences in immunity to HIV-1.

Recent findings: Prominent sex differences exist in various infectious and autoimmune diseases. Biological mechanisms underlying these differences include the modulation of immunological pathways by sex hormones and gene dosage effects of immunomodulatory genes encoded by the X chromosome. During HIV-1 infections, women have been shown to present with lower viral load levels in primary infection, although their progression to AIDS is faster in comparison with men when accounting for viral load levels in chronic infection. HIV-1-infected women furthermore tend to have higher levels of immune activation and interferon-stimulated gene expression in comparison with men for the same viral load, which has been associated to innate sensing of HIV-1 by Toll-like receptor 7 and the consequent interferon-α production by plasmacytoid dendritic cells.

Summary: Improvement in understanding the mechanisms associated with sex differences in HIV-1-mediated immunopathology will be critical to take sex differences into consideration when designing experimental and clinical studies in HIV-1-infected populations.

Figure 1. Direct and indirect sex-specific determinants modulate viral recognition and immune activation

In additional to environmental factors, X chromosome gene dosage and sex hormones can influence immune cell function, including innate sensing of viral components, type I IFN production and immune activation.