Gender differences in innate responses and gene expression profiles in memory CD4 T cells are apparent very early during acute simian immunodeficiency virus infection

PLoS One. 2019 Sep 6;14(9):e0221159. doi: 10.1371/journal.pone.0221159. eCollection 2019.

Abstract

Gender differences in Human immunodeficiency virus (HIV) disease progression and comorbidities have been extensively reported. Using the simian immunodeficiency virus (SIV) infected rhesus macaque model, we show that these differences are apparent very early during the course of infection. Though there were no major changes in the proportions of CD4 T cells or its subsets, central memory CD4 T cells from female macaques were found to differentially regulate a significantly larger number of genes at day 4 post-infection (PI) as compared to males. Pathway analysis revealed divergence of both canonical and biological pathways that persisted at day 10 PI. Changes in gene expression profiles were accompanied by a significant increase in plasma levels of pro-inflammatory mediators such as MCP-1/CCL2, I-TAC/CXCL11, and MIF. Though plasma levels of IFNα did not differ between male and female macaques, the expression levels of IFNα subtype-14, 16, IFNβ, and IFNω were significantly upregulated in the lymph nodes of female macaques at day 10 PI as compared to male macaques. Our results suggest that the pathogenic sequelae seen during chronic infection may be shaped by gender differences in immune responses induced very early during the course of HIV infection.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute Disease
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Chemokine CXCL11 / blood
  • Female
  • Gene Expression Profiling*
  • Immunity, Innate*
  • Interferons / blood
  • Macaca mulatta
  • Male
  • RNA, Messenger / genetics
  • Receptors, CCR2 / blood
  • Sex Characteristics*
  • Simian Acquired Immunodeficiency Syndrome / blood
  • Simian Acquired Immunodeficiency Syndrome / genetics*
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Acquired Immunodeficiency Syndrome / physiopathology
  • Simian Immunodeficiency Virus / physiology*

Substances

  • Chemokine CXCL11
  • RNA, Messenger
  • Receptors, CCR2
  • Interferons

Grants and funding

Funded by JJM. R0731976. Uniformed Services University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.