Protective immunity against mouse upper genital tract pathology correlates with high IFNγ but low IL-17 T cell and anti-secretion protein antibody responses induced by replicating chlamydial organisms in the airway

Abstract

To search for optimal immunization conditions for inducing protective immunity against upper genital tract pathologies caused by chlamydial intravaginal infection, we compared protection efficacy in mice immunized intranasally or intramuscularly with live or inactivated C. muridarum organisms. Mice immunized intranasally with live organisms developed strong protection against both vaginal shedding of infectious organisms and upper genital tract pathologies. The protection correlated with a robust antigen-specific T cell response with high IFNγ but low IL-17. Although a significant level of IL-5 was also detected, these mice maintained an overall Th1-dorminant immunity following immunization and challenge infection. On the contrary, mice immunized intranasally with inactivated organisms or intramuscularly with live or inactivated organisms produced high levels of IL-17 and still developed significant upper genital tract pathologies. High titers of antibodies against chlamydial secretion antigens were detected only in mice immunized intranasally with live organisms but not mice in other groups, suggesting that the intranasally inoculated live organisms were able to undergo replication and immune responses to the chlamydial secretion proteins may contribute to protective immunity. These observations have provided important information on how to develop subunit vaccines for inducing protective immunity against urogenital infection with C. trachomatis organisms.

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“…[8] However,Lu et al have shown that defense from genital infection by means of live Chlamydia immunization correlates with Т-cell response and is characterized by IFNγ high level and IL-17 low level. [9] Andrew et al in their investigation have illustrated that, in IL-17 absence, clinical gravity in chlamydial genital lesions is considerably lessened; [10] like this, in our study, IL-17 level in the chlamydial infection group was not different from the control values.…”

Reduced Live Organism Recovery and Lack of Hydrosalpinx in Mice Infected with Plasmid-Free Chlamydia muridarum

“…Each mouse was inoculated intravaginally with 2 ϫ 10 5 inclusion-forming units (IFU) of live C. muridarum plasmid-competent Nigg or plasmid-free CMUT3 organisms in 20 l of SPG (sucrose-phosphate-glutamate buffer) or intrabursally with different amounts of organisms, as indicated, in 10 l of SPG. For some experiments, plasmid-competent C. muridarum organisms were UV inactivated as described previously (17,18) before inoculation. Five days prior to infection, each mouse was injected subcutaneously with 2.5 mg Depo-Provera (Pharmacia Upjohn, Kalamazoo, MI) to synchronize the estrus cycle and increase mouse susceptibility to chlamydial infection.…”

Chlamydia muridarum Induction of Glandular Duct Dilation in Mice

“…Thus, it is necessary to characterize the C. muridarum-induced uterine horn dilation. Many previous mouse model-based studies grouped both hydrosalpinx and uterine horn dilation as upper genital tract pathology (19,20) and focused only on the fertility outcome (21)(22)(23) or patency of the upper genital tract (6) without differentiating uterine horn dilation from hydrosalpinx (8,(24)(25)(26)(27)(28). Although a previous study reported that interferon regulatory transcription factor 3 (IRF3) protected mice from uterine horn pathology during C. muridarum infection (13) and efforts have also been made to define host factors involved in C. muridarum induction of uterine horn dilation (29), the pathological basis of uterine horn dilation remains unclear.…”