Publications

Immunity to Mycobacterium tuberculosis in humans and in mice requires interferon gamma (IFN-gamma). Whereas IFN-gamma has been studied extensively for its effects on macrophages in tuberculosis, we determined that protective immunity to tuberculosis also requires IFN-gamma-responsive nonhematopoietic cells. Bone marrow chimeric mice with IFN-gamma-unresponsive lung epithelial and endothelial cells exhibited earlier mortality and higher bacterial burdens than control mice, underexpressed indoleamine-2,3-dioxygenase (Ido1) in lung endothelium and epithelium, and overexpressed interleukin-17 (IL-17) with massive neutrophilic inflammation in the lungs. We also found that the products of IDO catabolism of tryptophan selectively inhibit IL-17 production by Th17 cells, by inhibiting the action of IL-23. These results reveal a previously unsuspected role for IFN-gamma responsiveness in nonhematopoietic cells in regulation of immunity to M. tuberculosis and illustrate the role of IDO in the inhibition of Th17 cell responses.

BACKGROUND

Limited data exist on the risk of Chlamydia trachomatis and Neisseria gonorrhoeae transmission from oropharynx to urethra. We examined urethral C. trachomatis and N. gonorrhoeae positivity among men who have sex with men (MSM) seen at San Francisco City Clinic (San Francisco, CA) during 2007.

METHODS

All patients who sought care at the San Francisco City Clinic (the only municipal sexually transmitted disease clinic in San Francisco) received a standardized interview conducted by clinicians. We estimated urethral C. trachomatis and N. gonorrhoeae positivity for 2 groups of visits by MSM who visited during 2007: (1) men who reported their only urethral exposure was receiving fellatio in the previous 3 months and (2) men who reported unprotected insertive anal sex in the previous 3 months. Additionally, urethral C. trachomatis and N. gonorrhoeae positivity was estimated, stratified by human immunodeficiency virus infection status, urogenital symptom history, and whether the patient had been a contact to a sex partner with either chlamydia or gonorrhea.

RESULTS

Among MSM who reported only receiving fellatio, urethral C. trachomatis and N. gonorrhoeae positivity were 4.8% and 4.1%, respectively. These positivity estimates were similar to positivity found among MSM who reported unprotected insertive anal sex.

CONCLUSIONS

A more complete understanding of the risks of transmission of C. trachomatis and N. gonorrhoeae from oropharynx to urethra will help inform prevention and screening programs.