Mouse strain-dependent differences in susceptibility to Neisseria gonorrhoeae infection and induction of innate immune responses.
Acute gonorrhea in women is characterized by a mucopurulent exudate that contains polymorphonuclear leukocytes (PMNs) with intracellular gonococci. Asymptomatic infections are also common. Information on the innate response to Neisseria gonorrhoeae in women is limited to studies with cultured cells, isolated immune cells, and analyses of cervicovaginal fluids. 17beta-Estradiol-treated BALB/c mice can be experimentally infected with N. gonorrhoeae, and a vaginal PMN influx occurs in 50 to 80% of mice. Here, we compared the colonization loads and proinflammatory responses of BALB/c, C57BL/6 and C3H/HeN mice to N. gonorrhoeae. BALB/c and C57BL/6 mice were colonized at similar levels following inoculation with 10(6) CFU of N. gonorrhoeae. BALB/c, but not C57BL/6, mice exhibited a marked vaginal PMN influx. Tumor necrosis factor alpha, interleukin-6, macrophage inflammatory protein 2 (MIP-2), and keratinocyte-derived chemokine were elevated in vaginal secretions from infected BALB/c mice, but not in those from C57BL/6 mice. MIP-2 levels positively correlated with a vaginal PMN influx. In contrast to BALB/c and C57BL/6 mice, C3H/HeN mice were resistant to infection, and there was no evidence of an inflammatory response. We conclude that N. gonorrhoeae causes a productive infection in BALB/c mice that is characterized by the induction of proinflammatory cytokines and chemokines and the recruitment of PMNs. Infection of C57BL/6 mice, in contrast, is more similar to asymptomatic infection. C3H/HeN mice are inherently resistant to N. gonorrhoeae infection, and this resistance is not due to an overwhelming inflammatory response to infection. Host genetic factors can therefore impact susceptibility and the immune response to N. gonorrhoeae.
Packiam
Mathanraj
M
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799, USA.
Veit
Sandra J
SJ
Anderson
Deborah J
DJ
Ingalls
Robin R
RR
Jerse
Ann E
AE
D000818:Animals; D005260:Female; D020022:Genetic Predisposition to Disease; D006069:Gonorrhea / Q000235:genetics* / Q000276:immunology*; D007113:Immunity, Innate; D007249:Inflammation; D051379:Mice; D008815:Mice, Inbred Strains; D009344:Neisseria gonorrhoeae / Q000276:immunology*; D014621:Vagina / Q000382:microbiology