CXCL9 and CXCL10 expression are critical for control of genital herpes simplex virus type 2 infection through mobilization of HSV-specific CTL and NK cells to the nervous system.
CXCL9 and CXCL10 mediate the recruitment of T lymphocytes and NK cells known to be important in viral surveillance. The relevance of CXCL10 in comparison to CXCL9 in response to genital HSV-2 infection was determined using mice deficient in CXCL9 (CXCL9-/-) and deficient in CXCL10 (CXCL10-/-) along with wild-type (WT) C57BL/6 mice. An increased sensitivity to infection was found in CXCL10-/- mice in comparison to CXCL9-/- or WT mice as determined by detection of HSV-2 in the CNS at day 3 postinfection. However, by day 7 postinfection both CXCL9-/- and CXCL10-/- mice possessed significantly higher viral titers in the CNS in comparison to WT mice consistent with mortality (18-35%) of these mice within the first 7 days after infection. Even though CXCL9-/- and CXCL10-/- mice expressed elevated levels of CCL2, CCL3, CCL5, and CXCL1 in the spinal cord in comparison to WT mice, there was a reduction in NK cell and virus-specific CD8+ T cell mobilization to this tissue, suggesting CXCL9 and CXCL10 are critical for recruitment of these effector cells to the spinal cord following genital HSV-2 infection. Moreover, leukocytes from the spinal cord but not from draining lymph nodes or spleens of infected CXCL9-/- or CXCL10-/- mice displayed reduced CTL activity in comparison to effector cells from WT mice. Thus, the absence of CXCL9 or CXCL10 expression significantly alters the ability of the host to control genital HSV-2 infection through the mobilization of effector cells to sites of infection.
Thapa
Manoj
M
Department of Microbiology, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA.
Welner
Robert S
RS
Pelayo
Rosana
R
Carr
Daniel J J
DJ
D000818:Animals; D002465:Cell Movement; D002490:Central Nervous System / Q000276:immunology*; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism*; D054370:Chemokine CXCL9 / Q000235:genetics / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006558:Herpes Genitalis / Q000276:immunology*; D018258:Herpesvirus 2, Human; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D018925:Chemokines; D016207:Cytokines