Sahoo Manoranjan, Lantier Louis, Re Fabio
Department of Microbiology & Immunology, Rosalind Franklin University of Medicine and Science, 3333, Green Bay Road, North Chicago, IL, 60064, USA.
Curr Top Microbiol Immunol. 2016;397:199-214. doi: 10.1007/978-3-319-41171-2_10.
Burkholderia pseudomallei is a Gram-negative flagellate bacterium that causes melioidosis, a disease endemic to Southeast Asia and other tropical regions. Following infection of macrophages and other non-phagocytic cell types, B. pseudomallei or B. thailandensis (a related species that causes disease in mice but not humans) are able to escape the phagosome and replicate in the host cell cytoplasm. Resistance to infection with Burkholderia is dependent on the Nlrp3 and Nlrc4 inflammasomes and the non-canonical caspase-11 inflammasome. Nlrc4 mediates protection through induction of pyroptosis in the early phase of infection. As the infection progresses and as IL-18-dependent IFNγ production increases, caspase-11-dependent pyroptosis acquires a preponderant protective role. Production of IL-1β and IL-18 during infection is primarily mediated by Nlrp3. IL-18 is essential for survival because of its ability to induce IFNγ production, which in turn activates macrophage microbicidal functions and primes for caspase-11 expression. In contrast, during melioidosis, IL-1β has deleterious effects due to excessive recruitment of neutrophils to the lung and consequent tissue damage.
类鼻疽伯克霍尔德菌是一种革兰氏阴性鞭毛菌，可引起类鼻疽，这是一种在东南亚和其他热带地区流行的疾病。在巨噬细胞和其他非吞噬细胞类型被感染后，类鼻疽伯克霍尔德菌或泰国伯克霍尔德菌（一种在小鼠中致病但在人类中不致病的相关菌种）能够逃离吞噬体并在宿主细胞质中复制。对伯克霍尔德菌感染的抵抗力取决于Nlrp3和Nlrc4炎性小体以及非经典的caspase-11炎性小体。Nlrc4通过在感染早期诱导细胞焦亡来介导保护作用。随着感染的进展以及依赖IL-18的IFNγ产生增加，依赖caspase-11的细胞焦亡获得主要的保护作用。感染期间IL-1β和IL-18的产生主要由Nlrp3介导。IL-18对生存至关重要，因为它能够诱导IFNγ产生，进而激活巨噬细胞的杀菌功能并引发caspase-11的表达。相反，在类鼻疽期间，IL-1β具有有害作用，因为它会导致中性粒细胞过度募集到肺部并随之造成组织损伤。
