A Dartmouth study led by Charles Wira, PhD, with first author Marta Rodriguez-Garcia, MD, PhD, found that some portions of the female reproductive tract (FRT) are more likely to be infected by HIV, particularly the ectocervix compared to the endometrium. The paper, "Phenotype and Susceptibility to HIV-infection of CD4+ Th17 Cells in the Human Female Reproductive Tract," was published in Mucosal Immunology.
"This variance is likely due to the increased presence of a specific type of lymphocyte, named CD4+ Th17 cells, which we found were irregularly distributed in FRT tissues and more likely to be infected by HIV compared to other CD4+ T cells," explains Rodriguez-Garcia. "We also found that the FRT from postmenopausal women contains more of these very susceptible cells compared to premenopausal women, suggesting postmenopausal women could be at higher risk to acquire HIV."
While most studies utilize cells from blood to understand HIV infection, the Wira team developed a protocol to isolate and characterize cells from the FRT, which are the very cells that will encounter the virus first during sexual transmission of HIV.
"Isolation of the cells from tissue allowed us to characterize the cells in ways that cannot be done using whole tissue," says Wira. "Our findings in identifying these cells and their distribution within the tract, as well as the differences between pre- and post-menopausal women, have application beyond the HIV field, since these cells are important for protection against fungal and bacterial infection, gynecological cancers, and are also involved in autoimmune disorders, and pregnancy."
Wira and Rodriguez-Garcia used shared resources at Dartmouth including flow cytometry to analyze many markers at once in the isolated cells. Tissue from the FRT was available through the Department of Pathology. Dartmouth's shared resources are available to outside investigators by arrangement.
Looking forward, Rodriguez-Garcia reports, "We now want to understand how sex hormones play a role in regulating HIV-target cells in the FRT and the mechanisms through which FRT cells protect against infection."
Wira is professor of physiology and neurobiology at Dartmouth's Geisel School of Medicine. His work in cancer is facilitated by Dartmouth's Norris Cotton Cancer at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., where he is a member of the Immunology & Cancer Immunotherapy Research Program. Rodriquez-Garcia is a post-doctoral research associate in Geisel's Department of Physiology & Neurobiology.
"Phenotype and Susceptibility to HIV-infection of CD4+ Th17 Cells in the Human Female Reproductive Tract," was funded by the National Institutes of Health grants AI102838, AI071761, and AI013541.
Source: Dartmouth-Hitchcock Norris Cotton Cancer Center