NALP3 is not necessary for early protection against experimental tuberculosis.
In vitro, Toll-like receptors (TLR)2, 4 and 9 as well as NOD-like receptor 2 critically determine macrophage responses to Mycobacterium tuberculosis (Mtb) infection. However, in low-dose experimental murine tuberculosis, single or multiple deficiencies in TLRs 2, 4, 9 or NOD2 have little, if any, impact on early mycobacterial growth containment, granuloma formation and survival. Here, we analyzed the relevance of NALP3, one component of the danger-signaling inflammasome, for (i) Mtb-induced cytokine secretion in vitro and in vivo, (ii) restriction of Mtb replication in infected organs and (iii) granuloma formation. In the absence of functional NALP3, there was no IL-1beta and IL-18 production in Mtb-infected dendritic cells and macrophages in vitro, whereas secretion of IL-1alpha, IL-12p40 and TNF remained unaffected. After three weeks of infection, NALP3-deficient as well as IL-18-deficient mice were as capable as wildtype mice of restricting Mtb loads at a plateau level within well-differentiated granulomas. In conclusion, despite its involvement in cytokine processing, NALP3 is not essential for induction of protective immunity to Mtb.
Walter
Kerstin
K
Division of Molecular Inflammation Medicine, Research Center Borstel, Borstel, Germany.
Hölscher
Christoph
C
Tschopp
Jürg
J
Ehlers
Stefan
S
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D048708:Cell Growth Processes / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006099:Granuloma / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D020382:Interleukin-18 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology* / Q000382:microbiology
D002352:Carrier Proteins; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse