Pathogenic, but Not Nonpathogenic, Rickettsia spp. Evade Inflammasome-Dependent IL-1 Responses To Establish an Intracytosolic Replication Niche.
Pathogenic, but Not Nonpathogenic, Rickettsia spp. Evade Inflammasome-Dependent IL-1 Responses To Establish an Intracytosolic Replication Niche.
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DOI：
10.1128/mbio.02918-21
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发表时间：
2021-02-22
期刊：
影响因子：
6.4
通讯作者：
Azad AF
中科院分区：
文献类型：
--
作者：
Voss OH;Cobb J;Gaytan H;Rivera Díaz N;Sanchez R;DeTolla L;Rahman MS;Azad AF
立克（SPP。）是严格的细胞内细菌，其中一些是他们的哺乳动物宿主，包括人类的一个关键特征。难以捉摸show that disease severity in wild-type (WT) C57BL/6J mice infected with Rickettsia typhi (the etiologic agent of murine typhus) and Rickettsia rickettsii (the etiologic agent of Rocky Mountain spotted fever), but not with the nonpathogenic species Rickettsia montanensis, correlated with levels of bacteria burn as detected in the spleens of mice, as well as the serum concentrations of proinflammatory cytokine interleukin-1α (IL-1α) and, to a较小的IL-1β。 SII，但不是非致病性R. Montanensis，通过caspase-11 – apasdermin d（GSDMD）依赖性途径，诱导的诱导率主要从减少的IL-1α分泌中受益，以促进IL-1α分泌，以识别该疗程，以识别rickicsi rickicsi rickicsisiby， ogenic，与非致病性的人力体相同，优先针对CASPASE-11-GSDMD – IL-1α信号轴巨噬细胞中的轴，从而支持其在宿主中的复制。
Rickettsia species (spp.) are strict obligate intracellular bacteria, some of which are pathogenic in their mammalian host, including humans. One critical feature of these stealthy group of pathogens is their ability to manipulate hostile cytosolic environments to their benefits. Although our understanding of Rickettsia cell biology and pathogenesis is evolving, the mechanisms by which pathogenic Rickettsia spp. evade host innate immune detection remain elusive. Here, we show that disease severity in wild-type (WT) C57BL/6J mice infected with Rickettsia typhi (the etiologic agent of murine typhus) and Rickettsia rickettsii (the etiologic agent of Rocky Mountain spotted fever), but not with the nonpathogenic species Rickettsia montanensis, correlated with levels of bacterial burden as detected in the spleens of mice, as well as the serum concentrations of proinflammatory cytokine interleukin-1α (IL-1α) and, to a lesser extent, IL-1β. Antibody-mediated neutralization of IL-1α confirmed a key role in controlling mortality rates and bacterial burdens of rickettsia-infected WT mice. As macrophages are a primary source of both IL-1α and IL-1β cytokines, we determined the mechanism of the antirickettsial activities using bone marrow-derived macrophages. We found that pathogenic R. typhi and R. rickettsii, but not nonpathogenic R. montanensis, eluded pro-IL-1α induction and benefited predominantly from the reduced IL-1α secretion, via a caspase-11–gasdermin D (Gsdmd)-dependent pathway, to facilitate intracytosolic replication. Adoptive transfer experiments identified that IL-1α secretion by macrophages was critical for controlling rickettsiosis in WT mice. In sum, we identified a previously unappreciated pathway by which pathogenic, unlike nonpathogenic, rickettsiae preferentially target the caspase-11–Gsdmd–IL-1α signaling axis in macrophages, thus supporting their replication within the host.
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影响因子：
7
作者：
Place DE;Kanneganti TD
通讯作者：
Kanneganti TD
影响因子：
6.7
作者：
Rahman MS;Gillespie JJ;Kaur SJ;Sears KT;Ceraul SM;Beier-Sexton M;Azad AF
通讯作者：
Azad AF
影响因子：
15.1
作者：
Peters, Vanessa A.;Joesting, Jennifer J.;Freund, Gregory G.
通讯作者：
Freund, Gregory G.
影响因子：
6.4
作者：
Lehman, Stephanie S.;Noriea, Nicholas F.;Hackstadt, Ted
通讯作者：
Hackstadt, Ted
影响因子：
30.3
作者：
Mitchell G;Isberg RR
通讯作者：
Isberg RR