TY - JOUR
T1 - T cell response kinetics determines neuroinfection outcomes during murine HSV infection
AU - Lee, Aisha G.
AU - Scott, Jason M.
AU - Fabbrizi, Maria Rita
AU - Jiang, Xiaoping
AU - Sojka, Dorothy K.
AU - Miller, Mark J.
AU - Baldridge, Megan T.
AU - Yokoyama, Wayne M.
AU - Shin, Haina
N1 - Funding Information:
We thank Adjoa Cofie for technical assistance, and we thank Michael Diamond and Akiko Iwasaki for critical review of the manuscript. This research was supported by funding from the NIH (AI134962). AGL is supported by funding for the Training Program in Immunology from the NIH (T32 AI007163).
Publisher Copyright:
Copyright: © 2020, American Society for Clinical Investigation.
PY - 2020/3/12
Y1 - 2020/3/12
N2 - Herpes simplex virus-2 (HSV-2) and HSV-1 both can cause genital herpes, a chronic infection that establishes a latent reservoir in the nervous system. Clinically, the recurrence frequency of HSV-1 genital herpes is considerably less than HSV-2 genital herpes, which correlates with reduced neuronal infection. The factors dictating the disparate outcomes of HSV-1 and HSV-2 genital herpes are unclear. In this study, we show that vaginal infection of mice with HSV-1 leads to the rapid appearance of mature DCs in the draining lymph node, which is dependent on an early burst of NK cell-mediated IFN-γ production in the vagina that occurs after HSV-1 infection but not HSV-2 infection. Rapid DC maturation after HSV-1 infection, but not HSV-2 infection, correlates with the accelerated generation of a neuroprotective T cell response and early accumulation of IFN-γ-producing T cells at the site of infection. Depletion of T cells or loss of IFN-γ receptor (IFN-γR) expression in sensory neurons both lead to a marked loss of neuroprotection only during HSV-1, recapitulating a prominent feature of HSV-2 infection. Our experiments reveal key differences in host control of neuronal HSV-1 and HSV-2 infection after genital exposure of mice, and they define parameters of a successful immune response against genital herpes.
AB - Herpes simplex virus-2 (HSV-2) and HSV-1 both can cause genital herpes, a chronic infection that establishes a latent reservoir in the nervous system. Clinically, the recurrence frequency of HSV-1 genital herpes is considerably less than HSV-2 genital herpes, which correlates with reduced neuronal infection. The factors dictating the disparate outcomes of HSV-1 and HSV-2 genital herpes are unclear. In this study, we show that vaginal infection of mice with HSV-1 leads to the rapid appearance of mature DCs in the draining lymph node, which is dependent on an early burst of NK cell-mediated IFN-γ production in the vagina that occurs after HSV-1 infection but not HSV-2 infection. Rapid DC maturation after HSV-1 infection, but not HSV-2 infection, correlates with the accelerated generation of a neuroprotective T cell response and early accumulation of IFN-γ-producing T cells at the site of infection. Depletion of T cells or loss of IFN-γ receptor (IFN-γR) expression in sensory neurons both lead to a marked loss of neuroprotection only during HSV-1, recapitulating a prominent feature of HSV-2 infection. Our experiments reveal key differences in host control of neuronal HSV-1 and HSV-2 infection after genital exposure of mice, and they define parameters of a successful immune response against genital herpes.
UR - http://www.scopus.com/inward/record.url?scp=85082833767&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.134258
DO - 10.1172/jci.insight.134258
M3 - Article
C2 - 32161194
AN - SCOPUS:85082833767
SN - 2379-3708
VL - 5
JO - JCI Insight
JF - JCI Insight
IS - 5
M1 - e134258
ER -