Differential cellular immune responses against Orientia tsutsugamushi Karp and Gilliam strains following acute infection in mice
Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B569
Abstract ID: 4427
Presenting Author:
Lynn Soong , Professor at Univ. of Texas Med. Br., Galveston
Abstract:
Human infection with Orientia tsutsugamushi (Ot), an obligate intracellular bacterium, can be life threatening, due to pulmonary involvement and vascular parasitism. Yet, detailed studies of Ot strain-related immune responses in patients or animal models of infection are lacking. Here, we used two clinically prevalent bacterial strains to reveal cellular immunity in inflamed lungs and potential biomarkers of disease severity. While outbred CD-1 mice were highly susceptible to both Karp and Gilliam strains, C57BL/6 mice were susceptible to Karp but resistant to Gilliam; host susceptibility corresponded to tissue bacterial burdens and lung pathology. Flow cytometric analyses of perfused mouse lungs revealed robust and sustained influx and activation of innate immune cells (macrophages, neutrophils, NK cells), followed by CD4+ and CD8+ T cells, during Karp infection, but such responses were greatly attenuated during Gilliam infection. The robust cellular responses in Karp-infected mice positively correlated with significantly early and high levels of serum cytokine/chemokine protein levels (CXCL1, CCL2/3/5), as well as pulmonary gene expression (Cxcl1/2, Ccl2/3/4). Infection of mouse-derived primary macrophages also revealed bacterial strain-dependent immune gene expression profiles. Our lung- and macrophage-focused studies provided the first lines of evidence for differential cellular immune responses during scrub typhus progression in inbred and outbred mouse models.
Differential cellular immune responses against Orientia tsutsugamushi Karp and Gilliam strains following acute infection in mice
Category
Poster and Podium (Block Symposium)