In:
Infection and Immunity, American Society for Microbiology, Vol. 84, No. 12 ( 2016-12), p. 3379-3387
Abstract:
Scrub typhus is a potentially lethal infection that is caused by the obligate intracellular bacterium Orientia tsutsugamushi . The roles of Toll-like receptor 2 (TLR2) and TLR4 in innate recognition of O. tsutsugamushi have not been elucidated. By overexpression of TLR2 or TLR4 in HEK293 cells, we demonstrated that TLR2, but not TLR4, recognizes heat-stable compounds of O. tsutsugamushi that were sensitive to treatment with sodium hydroxide, hydrogen peroxide, and proteinase K. TLR2 was required for the secretion of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) by dendritic cells. In an intradermal mouse infection model, TLR2-deficient mice did not show impaired control of bacterial growth or reduced survival. Moreover, after intraperitoneal infection, TLR2-deficient mice were even more resistant to lethal infection than C57BL/6 wild-type mice, which showed stronger symptoms and lower survival rates during the convalescent phase. Compared to the time of reduction of bacterial loads in TLR2-deficient mice, the reduction of bacterial loads in infected organs was accelerated in wild-type mice. The higher mortality of wild-type mice was associated with increased concentrations of serum alkaline phosphatase but not aspartate aminotransferase. The transcription of mRNA for TNF-α and IL-6 decreased more rapidly in peritoneum samples from wild-type mice than in those from TLR2-deficient mice and was therefore not a correlate of increased susceptibility. Thus, although TLR2 is an important mediator of the early inflammatory response, it is dispensable for protective immunity against O. tsutsugamushi . Increased susceptibility to O. tsutsugamushi infection in TLR2-competent mice rather suggests a TLR2-related immunopathologic effect.
Type of Medium:
Online Resource
ISSN:
0019-9567
,
1098-5522
DOI:
10.1128/IAI.00185-16
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2016
detail.hit.zdb_id:
1483247-1
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