Chlamydia muridarum evades growth restriction by the IFN-gammainducible host resistance factor Irgb10

Chlamydiae are obligate intracellular bacterial pathogens that exhibit a broad range of host tropism. Differences in host tropism between Chlamydia species have been linked to host variations in IFN--mediated immune responses. In mouse cells, IFN- can effectively restrict growth of the human pathogen Chlamydia trachomatis but fails to control growth of the closely related mouse pathogen Chlamydia muridarum. The ability of mouse cells to resist C. trachomatis replication is largely dependent on the induction of a family of IFN--inducible GTPases called immunity-related GTPases or IRGs. In this study we demonstrate that C. muri-darum can specifically evade IRG-mediated host resistance. It has previously been suggested that C. muridarum inactivates the IRG protein Irga6 (Iigp1) to dampen the murine immune response. However, we show that Irga6 is dispensable for the control of C. trachomatis replication. Instead, an effective IFN- response to C. trachomatis requires the IRG proteins Irgm1 (Lrg47), Irgm3 (Igtp), and Irgb10. Ectopic expression of Irgb10 in the absence of IFN- is sufficient to reduce intracellular growth of C. tracho-matis but fails to restrict growth of C. muridarum, indicating that C. muridarum can specifically evade Irgb10-driven host re-sponses. Importantly, we find that Irgb10 protein intimately associates with inclusions harboring C. trachomatis but is absent from inclusions formed by C. muridarum. These data suggest that C. muridarum has evolved a mechanism to escape the murine IFN- response by restricting access of Irgb10 and possibly other IRG proteins to the inclusion. The Journal of Immunology, 2008, 180: 6237–6245. C hlamydia trachomatis is an obligate intracellular bacte-rial pathogen that is the etiologic agent of prevalent hu-man infections causing serious public health problem