The caspase 1 inflammasome is not required for control of murine Lyme borreliosis.
The contribution of the inflammasome to the development of immune responses and disease during infection with the Lyme disease spirochete, Borrelia burgdorferi, is not well defined. Host defense against the spirochete is severely impaired in mice deficient in the adaptor molecule myeloid differentiation antigen 88 (MyD88), which is required not only for Toll-like receptor-mediated responses but also for the production of the proforms of interleukin 1beta (IL-1beta) and IL-18. These cytokines are released in active forms after cleavage by the inflammasome-associated enzyme caspase 1. To investigate the contribution of the inflammasome to host defense against B. burgdorferi, we examined Lyme borreliosis in mice deficient in either caspase 1 or apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), a molecule upstream of caspase 1 in the inflammasome signaling cascade. We found that caspase 1-deficient mice had a mild transient elevation in pathogen burden and a trend toward an increase in the prevalence of arthritis early in infection, but these differences resolved by day 14 postinfection. Caspase 1 deficiency had no effect on B. burgdorferi-induced humoral immunity, T-cell responses, or the abilities of macrophages to ingest and degrade spirochetes. The absence of the ASC protein had no effect on the control of the spirochete or the development of immune responses and disease. These findings reveal that the caspase 1 inflammasome is not critical to host defense against the extracellular pathogen Borrelia burgdorferi.
Liu
Nengyin
N
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Belperron
Alexia A
AA
Booth
Carmen J
CJ
Bockenstedt
Linda K
LK
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D051017:Apoptosis Regulatory Proteins; D025065:Borrelia burgdorferi / Q000276:immunology*; D053468:CARD Signaling Adaptor Proteins; D020170:Caspase 1 / Q000172:deficiency / Q000276:immunology*; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000276:immunology; D005260:Female; D007249:Inflammation / Q000473:pathology*; D018664:Interleukin-12 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008193:Lyme Disease / Q000276:immunology* / Q000473:pathology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology
D000907:Antibodies, Bacterial; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; D053583:Interleukin-1beta; C498534:Pycard protein, mouse; D018664:Interleukin-12; D020170:Caspase 1