Inflammasome gene expression is associated with immunopathology in human localized cutaneous leishmaniasis

Gupta, Gaurav; Santana, Alynne Karen Mendonça de; Gomes, Ciro Martins; Turatti, Aline; Milanezi, Cristiane M.; Filho, Roberto Bueno; Fuzo, Carlos Alessandro; Almeida, Roque Pacheco de; Carregaro, Vanessa; Roselino, Ana Maria Ferreira; Silva, João

doi:10.1016/j.cellimm.2019.04.008

Cited by 21 publications

(11 citation statements)

References 49 publications

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“…Abrogation of inflammasome priming in vivo likely has important consequences for parasite survival and anti-microbial immunity, given the role of NLRP3 activation and IL-1b secretion in restricting parasite load and lesion development (Lima-Junior et al, 2013). This may underlie the non-inflammatory, anergic diffuse form of leishmaniasis caused by L. am (Christensen et al, 2019;Scorza et al, 2017) in contrast to nonhealing lesions that were associated with inflammasome activation (Charmoy et al, 2016;Gupta et al, 2019;Lee et al, 2018;Moreira et al, 2017). Although the parasite effector mechanisms causing host cell immune suppression remain elusive and may involve various parasite-or host-derived signals, including anti-inflammatory cytokines such as IL-10 (Conaway et al, 2017), our study draws a detailed and complex picture of their impact on the host cell phenotype.…”

Section: Discussionmentioning

confidence: 99%

Targeting Macrophage Histone H3 Modification as a Leishmania Strategy to Dampen the NF-κB/NLRP3-Mediated Inflammatory Response

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Targeting Macrophage Histone H3 Modification as a Leishmania Strategy to Dampen the NF-κB/NLRP3-Mediated Inflammatory Response

et al. 2020

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“…In a murine model of leishmaniasis, Aim2 has been shown to suppress pathogen control and promote tissue inflammation. 54 Toxoplasma gondii has also been reported to activate the AIM2 inflammasome, interestingly the outcome of which is an atypical caspase-8-dependent apoptosis rather than caspase-1-dependent pyroptosis. 27…”

Section: Anti-fungal and Anti-protozoan Host Defensementioning

confidence: 99%

AIM2 in health and disease: Inflammasome and beyond

Kumari

Russo

Shivcharan

et al. 2020

Immunological Reviews

157

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Nucleic acid sensing is a critical mechanism by which the immune system monitors for pathogen invasion. A set of germline‐encoded innate immune receptors detect microbial DNA in various compartments of the cell, such as endosomes, the cytosol, and the nucleus. Sensing of microbial DNA through these receptors stimulates, in most cases, interferon regulatory factor‐dependent type I IFN synthesis followed by JAK/STAT‐dependent interferon‐stimulated gene expression. In contrast, the detection of DNA in the cytosol by AIM2 assembles a macromolecular complex called the inflammasome, which unleashes the proteolytic activity of a cysteine protease caspase‐1. Caspase‐1 cleaves and activates the pro‐inflammatory cytokines such as IL‐1β and IL‐18 and a pore‐forming protein, gasdermin D, which triggers pyroptosis, an inflammatory form of cell death. Research over the past decade has revealed that AIM2 plays essential roles not only in host defense against pathogens but also in inflammatory diseases, autoimmunity, and cancer in inflammasome‐dependent and inflammasome‐independent manners. This review discusses the latest advancements in our understanding of AIM2 biology and its functions in health and disease.

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“…A study by Gupta et al 52 showed that skin biopsies from L braziliensis ‐infected human localized cutaneous leishmaniasis (LCL) patients have increased mRNA transcript levels of NLRP3, IL‐1β, and other inflammasome‐associated markers including caspase‐1, AIM2, and NLRP1. Importantly, immunohistochemistry staining for NLRP3 and IL‐1β shows increased levels of these proteins in LCL biopsies compared to normal control skin biopsies 52 . In addition, several studies in mice have shown that Leishmania spp.…”

Section: Activation Of the Nlrp3 Inflammasome During Leishmania Spp mentioning

confidence: 99%

“…infection, the proposed mechanisms vary greatly. In support of a pathogenic role for inflammasome, NLRP1 and AIM2 inflammasomes have also been implicated to promote lesion development during L braziliensis infection 52,106 ; although the downstream mechanisms remain unexplored. Miltefosine, an FDA approved drug used for treating leishmaniasis, 107 inhibits LPS + ATP‐induced NLRP3 inflammasome activation and IL‐1β release—suggesting NLRP3 targeting may provide specific drug alternatives to the currently available drugs 108 .…”

Section: Perspectives and Conclusionmentioning

confidence: 99%

Reconciling protective and pathogenic roles of the NLRP3 inflammasome in leishmaniasis

Harrington

Gurung

2020

Immunological Reviews

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Leishmaniasis is a global health problem that affects more than 2 billion people worldwide. Recent advances in research have demonstrated critical roles for cytoplasmic sensors and inflammasomes during Leishmania spp. infection and pathogenesis. Specifically, several studies have focused on the role of nod‐like receptor family, pyrin domain‐containing protein 3 (NLRP3) inflammasome and inflammasome‐associated cytokines IL‐1β and IL‐18 in leishmaniasis. Despite these studies, our understanding of the priming and activation events that lead to NLRP3 inflammasome activation during Leishmania spp. infection is limited. Furthermore, whether NLRP3 plays a protective or pathogenic role during Leishmania spp. infection is far from resolved, with some studies showing a protective role and others showing a pathogenic role. In this review, we performed a critical review of the literature to provide a current update on priming and activating signals required for NLRP3 inflammasome activation during Leishmania spp. infection. Finally, we provide a thorough review of the literature to reconcile differences in the observed protective vs pathogenic roles of the NLRP3 inflammasome during Leishmania spp. infection.

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Inflammasome gene expression is associated with immunopathology in human localized cutaneous leishmaniasis

Cited by 21 publications

References 49 publications

Targeting Macrophage Histone H3 Modification as a Leishmania Strategy to Dampen the NF-κB/NLRP3-Mediated Inflammatory Response

Targeting Macrophage Histone H3 Modification as a Leishmania Strategy to Dampen the NF-κB/NLRP3-Mediated Inflammatory Response

AIM2 in health and disease: Inflammasome and beyond

Reconciling protective and pathogenic roles of the NLRP3 inflammasome in leishmaniasis

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