Virulence factors perforate the pathogen-containing vacuole to signal efferocytosis

Intracellular pathogens commonly reside within macrophages to find shelter from humoral defenses, but host cell death can expose them to the extracellular milieu. We find intracellular pathogens solve this dilemma by using virulence factors to generate a complement-dependent find-me signal that init...

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Bibliographic Details
Published in:Cell host & microbe 2022-02, Vol.30 (2), p.163-170.e6
Main Authors: Hiyoshi, Hirotaka, English, Bevin C., Diaz-Ochoa, Vladimir E., Wangdi, Tamding, Zhang, Lillian F., Sakaguchi, Miako, Haneda, Takeshi, Tsolis, Renée M., Bäumler, Andreas J.
Format: Article
Language:English
Subjects:
Brucella
complement
efferocytosis
macrophage
neutrophil
Phagocytosis
Salmonella
Type III Secretion Systems
Type IV Secretion Systems - metabolism
Vacuoles - metabolism
Virulence Factors
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Summary:Intracellular pathogens commonly reside within macrophages to find shelter from humoral defenses, but host cell death can expose them to the extracellular milieu. We find intracellular pathogens solve this dilemma by using virulence factors to generate a complement-dependent find-me signal that initiates uptake by a new phagocyte through efferocytosis. During macrophage death, Salmonella uses a type III secretion system to perforate the membrane of the pathogen-containing vacuole (PCV), thereby triggering complement deposition on bacteria entrapped in pore-induced intracellular traps (PITs). In turn, complement activation signals neutrophil efferocytosis, a process that shelters intracellular bacteria from the respiratory burst. Similarly, Brucella employs its type IV secretion system to perforate the PCV membrane, which induces complement deposition on bacteria entrapped in PITs. Collectively, this work identifies virulence factor-induced perforation of the PCV as a strategy of intracellular pathogens to generate a find-me signal for efferocytosis. [Display omitted] •Salmonella T3SS-2 functions in evading neutrophil-mediated host control•T3SS-2 impairs endo-lysosomal integrity of the Salmonella-containing vacuole (SCV)•SCV perforation triggers a complement-dependent find-me signal for efferocytosis•Efferocytosis shelters Salmonella entrapped in PITs from killing by neutrophils Hiyoshi et al. find that Salmonella uses T3SS-2 to perforate the phagosome of macrophages, thereby generating a complement-dependent find-me signal for efferocytosis by neutrophils. Efferocytosis of Salmonella entrapped in dying macrophages shelters the pathogen from the neutrophil respiratory burst, thereby enabling the pathogen to evade neutrophil-mediated host control.
ISSN:1931-3128
1934-6069
1934-6069
DOI:10.1016/j.chom.2021.12.001