Guanylate binding proteins promote caspase-11–dependent pyroptosis in response to cytoplasmic LPS (original) (raw)

“…Indeed, GBPs function as sensors of endolysosomal membrane integrity (56) and play an important role during both canonical and noncanonical inflammasome activation in response to infection by Gram-negative bacteria. GBPs can contribute to inflammasome activation by binding to and disrupting pathogen-containing vacuoles or bacteria themselves, thus enabling the detection of cytoplasmic LPS (28,34,(61)(62)(63). Whether GBPs might be recruited to vacuoles containing translocated microbial products but not pathogens themselves has not been investigated.…”

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“…Indeed, GBPs function as sensors of endolysosomal membrane integrity (56) and play an important role during both canonical and noncanonical inflammasome activation in response to infection by Gram-negative bacteria. GBPs can contribute to inflammasome activation by binding to and disrupting pathogen-containing vacuoles or bacteria themselves, thus enabling the detection of cytoplasmic LPS (28,34,(61)(62)(63). Whether GBPs might be recruited to vacuoles containing translocated microbial products but not pathogens themselves has not been investigated.…”

Section: Resultsmentioning

“…However, GBPs can also promote the activation of caspase-11 independent of direct vacuolar lysis in the case of Legionella or Chlamydia (28,33). In support of their lysis-independent function, GBPs were demonstrated to be important for noncanonical inflammasome activation in response to transfection of LPS into the cytosol (28).…”

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