Decreased vaginal disease in J-chain-deficient mice following herpes simplex type 2 genital infection.
J-chain-deficient (Jch(-/-)) mice were used to study the role of polymeric IgA (pIgA) in primary disease and protective immunity following genital herpes simplex type 2 (HSV-2) infection. Vaginal IgA in the Jch(-/-) mice was composed primarily of monomeric IgA and was not associated with secretory component (SC). In contrast, vaginal IgA in wild-type (WT) mice was predominantly polymeric and bound to SC. Following HSV-2 genital infection, the Jch(-/-) mice consistently exhibited fewer vaginal symptoms (P = 0.010) and mortality (P = 0.075) than did the WT mice. The variation in disease expression could not be explained by differences in local viral replication, since titers in vaginal wash fluid were comparable. To assess the effect of J chain deficiency on protective immunity, WT and Jch(-/-) mice were immunized intravaginally with attenuated HSV-2, challenged intravaginally with wild-type virus 5 weeks later, and evaluated for vaginal infection and neurological disease. Although the Jch(-/-) mice had reduced vaginal HSV-specific IgA and IgG levels following immunization, both WT and Jch(-/-) mice were protected from symptoms following wild-type virus challenge. We conclude that pIgA is not required for protective immunity against genital HSV-2 disease and that J chain deficiency offers some protection against symptoms following primary HSV-2 genital infection.
Hendrickson
B A
BA
Section of Pediatric Infectious Diseases, University of Chicago Children's Hospital, 5841 South Maryland Avenue, MC6054, Chicago, Illinois 60637, USA. bhendric@peds.bsd.uchicago.edu
Guo
J
J
Brown
I
I
Dennis
K
K
Marcellino
D
D
Hetzel
J
J
Herold
B C
BC
D000818:Animals; D004406:Dysgammaglobulinemia / Q000150:complications / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006558:Herpes Genitalis / Q000150:complications / Q000276:immunology*; D018258:Herpesvirus 2, Human; D007113:Immunity, Innate; D007070:Immunoglobulin A / Q000502:physiology*; D007144:Immunoglobulin J-Chains / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D014611:Vaccination; D014623:Vaginal Diseases / Q000276:immunology* / Q000821:virology
D007070:Immunoglobulin A; D007144:Immunoglobulin J-Chains; C034639:polymeric IgA