Involvement of Nod2 in the innate immune response elicited by malarial pigment hemozoin
Department of Medicine, Division of Infectious Disease & Immunology
Immunity | Immunology and Infectious Disease | Immunology of Infectious Disease | Infectious Disease | Parasitology
In malaria, the evidence concerning the nucleotide-binding, oligomerization domain (NOD) 2 (NOD2) receptor is fragmented and the stimuli that might activate NOD2 are not well characterized. We investigated the role of NOD2 in vitro in the response of macrophages to Plasmodium falciparum products. Immortalized or primary bone marrow derived macrophages from wild type C57Bl/6 mice, or knockout mice for NOD2 or its adaptor proteins, were either primed with interferon gamma or left untreated, and stimulated with parasite products. Both lysates of infected erythrocytes or hemozoin induced higher levels of nitric oxide in primed than in unprimed wild type macrophages. When stimulated with hemozoin, primed macrophages knockout for NOD2, or for its adaptor proteins, produced significantly lower nitric oxide levels compared to wild type cells. Differently from hemozoin, the use of beta-hematin (synthetic hemozoin) as stimulus showed that NOD2 is dispensable. Furthermore, the production of inflammatory cytokines by wild type cells treated with hemozoin was not dependent on NOD2. These data indicate that parasite components present in the hemozoin, differently from beta-hematin, induce the production of nitric oxide through the activation of NOD2, whereas the production of inflammatory cytokines, like TNF-alpha or MIP-2 (CXCL2), seems to be NOD2 independent. reserved.
DOI of Published Version
Microbes Infect. 2015 Mar;17(3):184-94. doi: 10.1016/j.micinf.2014.11.001. Link to article on publisher's site
Microbes and infection / Institut Pasteur
Corbett, Yolanda; Parapini, Silvia; D'Alessandro, Sarah; Scaccabarozzi, Diletta; Rocha, Bruno C.; Egan, Timothy J.; Omar, Aneesa; Galastri, Laura; Fitzgerald, Katherine A.; Golenbock, Douglas T.; Taramelli, Donatella; and Basilico, Nicoletta, "Involvement of Nod2 in the innate immune response elicited by malarial pigment hemozoin" (2015). Infectious Diseases and Immunology Publications and Presentations. 196.