Impact of asymptomatic herpes simplex virus type 2 infection on mucosal homing and immune cell subsets in the blood and female genital tract.
HSV-2 infection is common and generally asymptomatic, but it is associated with increased HIV susceptibility and disease progression. This may relate to herpes-mediated changes in genital and systemic immunology. Cervical cytobrushes and blood were collected from HIV-uninfected African/Caribbean women in Toronto, and immune cell subsets were enumerated blindly by flow cytometry. Immune differences between groups were assessed by univariate analysis and confirmed using a multivariate model. Study participants consisted of 46 women, of whom 54% were infected with HSV-2. T cell activation and expression of the mucosal homing integrin α4β7 (19.60 versus 8.76%; p < 0.001) were increased in the blood of HSV-2-infected women. Furthermore, expression of α4β7 on blood T cells correlated with increased numbers of activated (coexpressing CD38/HLA-DR; p = 0.004) and CCR5(+) (p = 0.005) cervical CD4(+) T cells. HSV-2-infected women exhibited an increase in the number of cervical CD4(+) T cells (715 versus 262 cells/cytobrush; p = 0.016), as well as an increase in the number and proportion of cervical CD4(+) T cells that expressed CCR5(+) (406 versus 131 cells, p = 0.001; and 50.70 versus 34.90%, p = 0.004) and were activated (112 versus 13 cells, p < 0.001; and 9.84 versus 4.86%, p = 0.009). Mannose receptor expression also was increased on cervical dendritic cell subsets. In conclusion, asymptomatic HSV-2 infection was associated with significant systemic and genital immune changes, including increased immune activation and systemic α4β7 expression; correlation of the latter with highly HIV-susceptible CD4(+) T cell subsets in the cervix may provide a mechanism for the increased HIV susceptibility observed in asymptomatic HSV-2-infected women.
Department of Medicine, University of Toronto, Toronto, Ontario M5G 2C4, Canada; Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; rupert.kaul@utoronto.ca brett.shannon@utoronto.ca.
Brett
B
Shannon
Department of Medicine, University of Toronto, Toronto, Ontario M5G 2C4, Canada; Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada;
Tae Joon
TJ
Yi
Women's Health in Women's Hands Community Health Centre, Toronto M5B 7J3, Ontario, Canada;
Jamie
J
Thomas-Pavanel
Women's Health in Women's Hands Community Health Centre, Toronto M5B 7J3, Ontario, Canada;
Lisungu
L
Chieza
Women's Health in Women's Hands Community Health Centre, Toronto M5B 7J3, Ontario, Canada;
Praseedha
P
Janakiram
Women's Health in Women's Hands Community Health Centre, Toronto M5B 7J3, Ontario, Canada;
Megan
M
Saunders
Women's Health in Women's Hands Community Health Centre, Toronto M5B 7J3, Ontario, Canada;
Wangari
W
Tharao
Department of Medicine, University of Toronto, Toronto, Ontario M5G 2C4, Canada; Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada;
Sanja
S
Huibner
Department of Epidemiology, University of Toronto, Toronto, Ontario M5T 3M7, Canada; Public Health Ontario - Toronto Public Health Laboratory, Toronto, Ontario M9P 3T1, Canada; and.
Robert
R
Remis
Department of Medicine, University of Toronto, Toronto, Ontario M5G 2C4, Canada; Public Health Ontario - Toronto Public Health Laboratory, Toronto, Ontario M9P 3T1, Canada; and.
Anu
A
Rebbapragada
Department of Medicine, University of Toronto, Toronto, Ontario M5G 2C4, Canada; Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; University Health Network, Toronto, Ontario M5G 2C4, Canada rupert.kaul@utoronto.ca brett.shannon@utoronto.ca.
Rupert
R
Kaul
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002584:Cervix Uteri / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006558:Herpes Genitalis / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D016023:Integrins; C071777:integrin alpha4beta7