Skip to main content
Immunology logoLink to Immunology
. 1998 Oct;95(2):208–213. doi: 10.1046/j.1365-2567.1998.00587.x

Immunity to vaginal HSV-2 infection in immunoglobulin A knockout mice.

M B Parr 1, G R Harriman 1, E L Parr 1
PMCID: PMC1364306  PMID: 9824477

Abstract

An immunoglobulin A (IgA) knockout (KO) mouse was used to study the role of IgA in protective immunity against vaginal infection with herpes simplex virus-type 2 (HSV-2). Intact and KO mice were immunized intravaginally (IVAG) with attenuated HSV-2, challenged IVAG with wild-type virus 6 weeks later and evaluated for vaginal infection and neurological disease. Non-immunized/challenged intact and KO mice showed vaginal infection and succumbed to neurological disease, while immunized/challenged mice exhibited reduced or no vaginal infection and no neurological disease. Log 2.5 enzyme-linked immunoassay (ELISA) titres of viral IgA, immunoglobulin G (IgG) and immunoglobulin M (IgM) in vaginal secretions collected from intact immune mice before challenge were 0.6+/-0.3, 6.4+/-0.32 and 0.0, while those in KO immune mice were 0.0, 6.7+/-0.19 and 3.0+/-0.29, respectively. Twenty-four hours after challenge, the percentage of vaginal epithelium that was infected in non-immune intact and KO mice was 2.0+/-0.6 and 2.4+/-0.6, which was reduced to 0.2+/-0.1 and 0.1+/-0.06 in immune intact and KO mice, respectively. No shed virus protein was detected in vaginal secretions 3 days after challenge in any immune mouse, whereas titres were 1400 and 1700 in the two groups of non-immune mice. Thus, immune protection against vaginal HSV-2 infection was similar in both KO and intact mice, indicating that this mucosal immunity does not depend mainly on IgA.

Full text

PDF
210

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ammann A. J., Hong R. Selective IgA deficiency: presentation of 30 cases and a review of the literature. Medicine (Baltimore) 1971 May;50(3):223–236. [PubMed] [Google Scholar]
  2. Brandtzaeg P., Gjeruldsen S. T., Korsrud F., Baklien K., Berdal P., Ek J. The human secretory immune system shows striking heterogeneity with regard to involvement of J chain-positive IgD immunocytes. J Immunol. 1979 Feb;122(2):503–510. [PubMed] [Google Scholar]
  3. Brandtzaeg P., Karlsson G., Hansson G., Petruson B., Björkander J., Hanson L. A. The clinical condition of IgA-deficient patients is related to the proportion of IgD- and IgM-producing cells in their nasal mucosa. Clin Exp Immunol. 1987 Mar;67(3):626–636. [PMC free article] [PubMed] [Google Scholar]
  4. Gallichan W. S., Rosenthal K. L. Effects of the estrous cycle on local humoral immune responses and protection of intranasally immunized female mice against herpes simplex virus type 2 infection in the genital tract. Virology. 1996 Oct 15;224(2):487–497. doi: 10.1006/viro.1996.0555. [DOI] [PubMed] [Google Scholar]
  5. Hermans P. E., Diaz-Buxo J. A., Stobo J. D. Idiopathic late-onset immunoglobulin deficiency. Clinical observations in 50 patients. Am J Med. 1976 Aug;61(2):221–237. doi: 10.1016/0002-9343(76)90173-x. [DOI] [PubMed] [Google Scholar]
  6. Holmgren J., Clemens J., Sack D. A., Sanchez J., Svennerholm A. M. Oral immunization against cholera. Curr Top Microbiol Immunol. 1989;146:197–204. doi: 10.1007/978-3-642-74529-4_21. [DOI] [PubMed] [Google Scholar]
  7. Kilian M., Mestecky J., Russell M. W. Defense mechanisms involving Fc-dependent functions of immunoglobulin A and their subversion by bacterial immunoglobulin A proteases. Microbiol Rev. 1988 Jun;52(2):296–303. doi: 10.1128/mr.52.2.296-303.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kuklin N., Daheshia M., Karem K., Manickan E., Rouse B. T. Induction of mucosal immunity against herpes simplex virus by plasmid DNA immunization. J Virol. 1997 Apr;71(4):3138–3145. doi: 10.1128/jvi.71.4.3138-3145.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lee E. J., Kaminchik J., Hankins W. D. Expression of xenotropic-like env RNA sequences in normal DBA/2 and NZB mouse tissues. J Virol. 1984 Jul;51(1):247–250. doi: 10.1128/jvi.51.1.247-250.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Liew F. Y., Russell S. M., Appleyard G., Brand C. M., Beale J. Cross-protection in mice infected with influenza A virus by the respiratory route is correlated with local IgA antibody rather than serum antibody or cytotoxic T cell reactivity. Eur J Immunol. 1984 Apr;14(4):350–356. doi: 10.1002/eji.1830140414. [DOI] [PubMed] [Google Scholar]
  11. Magnusson K. E., Stjernström I. Mucosal barrier mechanisms. Interplay between secretory IgA (SIgA), IgG and mucins on the surface properties and association of salmonellae with intestine and granulocytes. Immunology. 1982 Feb;45(2):239–248. [PMC free article] [PubMed] [Google Scholar]
  12. Mazanec M. B., Coudret C. L., Fletcher D. R. Intracellular neutralization of influenza virus by immunoglobulin A anti-hemagglutinin monoclonal antibodies. J Virol. 1995 Feb;69(2):1339–1343. doi: 10.1128/jvi.69.2.1339-1343.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McGhee J. R., Mestecky J. In defense of mucosal surfaces. Development of novel vaccines for IgA responses protective at the portals of entry of microbial pathogens. Infect Dis Clin North Am. 1990 Jun;4(2):315–341. [PubMed] [Google Scholar]
  14. Mellander L., Björkander J., Carlsson B., Hanson L. A. Secretory antibodies in IgA-deficient and immunosuppressed individuals. J Clin Immunol. 1986 Jul;6(4):284–291. doi: 10.1007/BF00917328. [DOI] [PubMed] [Google Scholar]
  15. Milligan G. N., Bernstein D. I. Generation of humoral immune responses against herpes simplex virus type 2 in the murine female genital tract. Virology. 1995 Jan 10;206(1):234–241. doi: 10.1016/s0042-6822(95)80038-7. [DOI] [PubMed] [Google Scholar]
  16. Nilssen D. E., Brandtzaeg P., Frøland S. S., Fausa O. Subclass composition and J-chain expression of the 'compensatory' gastrointestinal IgG cell population in selective IgA deficiency. Clin Exp Immunol. 1992 Feb;87(2):237–245. doi: 10.1111/j.1365-2249.1992.tb02981.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ogra P. L., Coppola P. R., MacGillivray M. H., Dzierba J. L. Mechanism of mucosal immunity to viral infections in gammaA immunoglobulin-deficiency syndromes. Proc Soc Exp Biol Med. 1974 Mar;145(3):811–816. doi: 10.3181/00379727-145-37900. [DOI] [PubMed] [Google Scholar]
  18. Parr E. L., Bozzola J. J., Parr M. B. Purification and measurement of secretory IgA in mouse milk. J Immunol Methods. 1995 Mar 27;180(2):147–157. doi: 10.1016/0022-1759(94)00310-s. [DOI] [PubMed] [Google Scholar]
  19. Parr E. L., Parr M. B. Immunoglobulin G is the main protective antibody in mouse vaginal secretions after vaginal immunization with attenuated herpes simplex virus type 2. J Virol. 1997 Nov;71(11):8109–8115. doi: 10.1128/jvi.71.11.8109-8115.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Parr E. L., Parr M. B. Immunoglobulin G, plasma cells, and lymphocytes in the murine vagina after vaginal or parenteral immunization with attenuated herpes simplex virus type 2. J Virol. 1998 Jun;72(6):5137–5145. doi: 10.1128/jvi.72.6.5137-5145.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Parr M. B., Kepple L., McDermott M. R., Drew M. D., Bozzola J. J., Parr E. L. A mouse model for studies of mucosal immunity to vaginal infection by herpes simplex virus type 2. Lab Invest. 1994 Mar;70(3):369–380. [PubMed] [Google Scholar]
  22. Parr M. B., Parr E. L. Mucosal immunity to herpes simplex virus type 2 infection in the mouse vagina is impaired by in vivo depletion of T lymphocytes. J Virol. 1998 Apr;72(4):2677–2685. doi: 10.1128/jvi.72.4.2677-2685.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Parr M. B., Parr E. L. Protective immunity against HSV-2 in the mouse vagina. J Reprod Immunol. 1997 Nov 30;36(1-2):77–92. doi: 10.1016/s0165-0378(97)00055-7. [DOI] [PubMed] [Google Scholar]
  24. Pereira L. F., Sapiña A. M., Arroyo J., Viñuelas J., Bardají R. M., Prieto L. Prevalence of selective IgA deficiency in Spain: more than we thought. Blood. 1997 Jul 15;90(2):893–893. [PubMed] [Google Scholar]
  25. Plebani A., Mira E., Mevio E., Monafo V., Notarangelo L. D., Avanzini A., Ugazio A. G. IgM and IgD concentrations in the serum and secretions of children with selective IgA deficiency. Clin Exp Immunol. 1983 Sep;53(3):689–696. [PMC free article] [PubMed] [Google Scholar]
  26. Underdown B. J., Schiff J. M. Immunoglobulin A: strategic defense initiative at the mucosal surface. Annu Rev Immunol. 1986;4:389–417. doi: 10.1146/annurev.iy.04.040186.002133. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES