Initial route of antigen administration alters the T-cell cytokine profile produced in response to the mouse pneumonitis biovar of Chlamydia trachomatis following genital infection

Abstract

A Th1-type response develops following vaginal infection with the mouse pneumonitis biovar of Chlamydia trachomatis (MoPn). Since the type of response, i.e., Th1 versus Th2, can be influenced by factors present during T-cell activation, we examined the effects of different routes of MoPn administration on the cytokine profile and resistance against infection following a MoPn vaginal challenge. A dominant Th1-type cytokine profile developed in mice given live MoPn via the intranasal, oral, and vaginal routes with ratios of gamma interferon-secreting cells to interleukin 4-secreting cells greater than 10. In contrast, mice injected subcutaneously produced a Th2-type profile with a gamma interferon/interleukin 4 ratio of only 0.7. These mice also had significantly higher anti-MoPn immunoglobulin G1 serum titers, confirming a Th2-type cytokine profile. Exposure of mice to live MoPn, by any route prior to vaginal challenge, resulted in a shortened course of infection. However, the subcutaneous group resolved the vaginal infection more slowly, with 60% (6 of 10 mice) of the mice still isolation positive 12 days after challenge compared with only 20% of mice given live MoPn by other routes. Administration of UV-inactivated MoPn did not provide protection against a vaginal challenge. The decreased ability to clear infection was not associated with a shift in the cytokine profile, since intranasal and oral administration of UV-inactivated MoPn resulted in a predominant Th1-type response. Taken together, these data indicate that the initial route of MoPn administration can direct the type of response produced after a local MoPn infection and thus influence the ability of the immune response to protect against subsequent infection.

Adjuvant is the Major Parameter Influencing the Isotype Profiles Generated During Immunization with a Protein Antigen, the Schistosoma mansoni Sm28‐GST

“…Subcutaneous administration of bacteria induced a more mixed type of response. In a recent study [36] it was also reported that the s.c. injection of the intracellular pathogen Chlamydia trachomatis generated a less polarized response than mucosal immunization that induced a Th1 profile. Since both organisms are intracellular pathogens, the cell types that are infected after s.c. administration may condition the establishment of a more balanced response.…”

Prostaglandin E2 modulates dendritic cell function during chlamydial genital infection

“…47 No obvious difference was observed in the numbers of DC subsets between PGE 2 and control mice in the spleen early after infection (data not shown) consistent with reports that the ILN is the primary site of T-cell activation early after infection in a genital infection. 48,49 These results imply that PGE 2 affects the migration of cDCs, but not pDCs, in vivo.…”

Chlamydial infection of the gastrointestinal tract: a reservoir for persistent infection

“…That the host does indeed respond to GI tract infection was noted by the presence of a strong local and systemic antibody response as well as a positive proliferation response in the MLN and ILN. Moreover, previous studies with oral immunization with viable organisms in both mouse and guinea pig models have demonstrated a substantial humoral and cell-mediated protective response to genital tract challenge (Nichols et al, 1978;Rank et al, 1990;Kelly et al, 1996). The absence of an inflammatory response in conjunction with clear evidence for active replication of chlamydiae as evidenced by successful isolation could be the result of numerous well-documented down-regulatory mechanisms elicited by other gut microbiota (Round & Mazmanian, 2009).…”

“…Regardless of the mechanisms by which chlamydiae survive in the local GI tract milieu, oral infection clearly activates an adaptive immune response that may manifest protection in other mucosal sites. In both mouse and guinea pig models, oral infection can elicit a protective response in the genital tract resulting in a shorter course of infection with lower peak infection levels (Nichols et al, 1978;Rank et al, 1990;Kelly et al, 1996). We noted many years ago that serum antibodies to all chlamydial antigens actually increased over time and that antibody to higher-molecular-weight proteins appeared consistently 90-100 days after infection (Ramsey et al, 1989).…”