Nitric Oxide Partially Controls<i>Coxiella burnetii</i>Phase II Infection in Mouse Primary Macrophages

Zamboni, Dario S.; Rabinovitch, M.

doi:10.1128/iai.71.3.1225-1233.2003

Cited by 113 publications

(106 citation statements)

References 42 publications

(47 reference statements)

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“…This transcriptional pattern of MU may account for C. burnetii infection in Vanin-1 -/-mice. First, MUderived NO inhibited C. burnetii replication [23]. In addition, iNOS inactivation is associated with decreased granuloma formation without alteration of their organization in a mouse model of tuberculosis [24], as in Vanin-1 -/-mice infected with C. burnetii.…”

Section: Discussionmentioning

confidence: 99%

Vanin‐1 controls granuloma formation and macrophage polarization in Coxiella burnetii infection

Meghari¹,

Berruyer-Pouyet²,

Lépidi³

et al. 2006

Eur J Immunol

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Q fever is caused by Coxiella burnetii, a bacterium that survives in MU. Vanin-1 is a membrane-anchored pantetheinase that controls tissue inflammation. Consequently, Vanin-1-deficient mice represent a unique mouse model in which stress-induced inflammation is limited by the reaction of resident tissue cells. To investigate the contribution of host tissues in the control of a bacterial infection, we infected Vanin-1-deficient mice with C. burnetii. Mortality and morbidity of mice were not affected. The lack of Vanin-1 had no effect on C. burnetii clearance but decreased the formation of granulomas in spleen and liver. Granuloma formation depends upon MU recruitment and activation in these tissues. Whereas the former was slightly impaired in mutant mice, the lack of Vanin-1 significantly affected the activation pattern of BM-derived MU stimulated by C. burnetii. While their microbicidal activity against C. burnetii was moderately impaired, they exhibited decreased inducible nitric oxide synthase (iNOS) and MCP-1 gene expression, and increased IL-10 and arginase expression. In liver from mutant mice, increased arginase expression and decreased expression of MCP-1 and iNOS were reminiscent of MU data. These results suggest a role of Vanin-1 in granuloma formation in response to C. burnetii by skewing MU activation toward an M2 program. See accompanying commentary http://dx

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Section: Discussionmentioning

confidence: 99%

Vanin‐1 controls granuloma formation and macrophage polarization in Coxiella burnetii infection

Meghari¹,

Berruyer-Pouyet²,

Lépidi³

et al. 2006

Eur J Immunol

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“…Preparation of Mouse Macrophages-Bone marrow-derived macrophages (BMDM) were prepared as described (19). Bone marrow cells were cultured for 7 days at 37°C in 5% CO 2 in RPMI 1640 medium supplemented with 30% L929 supernatant containing macrophage-stimulating factor, 10% heat-inactivated fetal calf serum (FCS), 10 mM HEPES, 1 mM sodium pyruvate, 2 mM L-glutamine, and 100 units/ml streptomycin and penicillin.…”

Section: Methodsmentioning

confidence: 99%

A Novel Pathway for Inducible Nitric-oxide Synthase Activation through Inflammasomes

Buzzo

Campopiano

Massis

et al. 2010

Journal of Biological Chemistry

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Innate immune recognition of flagellin is shared by transmembrane TLR5 and cytosolic Nlrc4 (NOD-like receptor family CARD (caspase activation recruitment domain) domain containing 4)/Naip5 (neuronal apoptosis inhibitory protein 5). TLR5 activates inflammatory genes through MYD88 pathway, whereas Nlrc4 and Naip5 assemble multiprotein complexes called inflammasomes, culminating in caspase-1 activation, IL-1␤/IL-18 secretion, and pyroptosis. Although both TLR5 and Naip5/Nlrc4 pathways cooperate to clear infections, little is known about the relative anti-pathogen effector mechanisms operating through each of them. Here we show that the cytosolic flagellin (FLA-BSDot) was able to activate iNOS, an enzyme previously associated with TLR5 pathway. Using Nlrc4-or Naip5-deficient macrophages, we found that both receptors are involved in iNOS activation by FLA-BSDot. Moreover, distinct from extracellular flagellin (FLA-BS), iNOS activation by intracellular flagellin is completely abrogated in the absence of caspase-1. Interestingly, IL-1␤ and IL-18 do not seem to be important for FLA-BSDot-mediated iNOS production. Together, our data defined an additional anti-pathogen effector mechanism operated through Naip5 and Nlrc4 inflammasomes and illustrated a novel signaling transduction pathway that activates iNOS.

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“…After 5 d of infection, the amount of released parasites was quantified using a Neubauer chamber. The NO production, 48 h postinfection, was estimated using the Griess reaction as described previously (23). For the in vivo experiments, the mice were infected i.p with 10 3 blood-derived trypomastigote forms of T. cruzi, and the mortality was monitored daily.…”

Section: Parasites and Infectionsmentioning

confidence: 99%

Apoptosis-Associated Speck–like Protein Containing a Caspase Recruitment Domain Inflammasomes Mediate IL-1β Response and Host Resistance to Trypanosoma cruzi Infection

Silva

Sesti-Costa

Silveira

et al. 2013

The Journal of Immunology

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The innate immune response to Trypanosoma cruzi infection comprises several pattern recognition receptors (PRRs), including TLR-2, -4, -7, and -9, as well as the cytosolic receptor Nod1. However, there are additional PRRs that account for the host immune responses to T. cruzi. In this context, the nucleotide-binding oligomerization domain–like receptors (NLRs) that activate the inflammasomes are candidate receptors that deserve renewed investigation. Following pathogen infection, NLRs form large molecular platforms, termed inflammasomes, which activate caspase-1 and induce the production of active IL-1β and IL-18. In this study, we evaluated the involvement of inflammasomes in T. cruzi infection and demonstrated that apoptosis-associated speck–like protein containing a caspase recruitment domain (ASC) inflammasomes, including NLR family, pyrin domain–containing 3 (NLRP3), but not NLR family, caspase recruitment domain–containing 4 or NLR family, pyrin domain–containing 6, are required for triggering the activation of caspase-1 and the secretion of IL-1β. The mechanism by which T. cruzi mediates the activation of the ASC/NLRP3 pathway involves K+ efflux, lysosomal acidification, reactive oxygen species generation, and lysosomal damage. We also demonstrate that despite normal IFN-γ production in the heart, ASC−/− and caspase-1−/− infected mice exhibit a higher incidence of mortality, cardiac parasitism, and heart inflammation. These data suggest that ASC inflammasomes are critical determinants of host resistance to infection with T. cruzi.

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Nitric Oxide Partially ControlsCoxiella burnetiiPhase II Infection in Mouse Primary Macrophages

Cited by 113 publications

References 42 publications

Vanin‐1 controls granuloma formation and macrophage polarization in Coxiella burnetii infection

Vanin‐1 controls granuloma formation and macrophage polarization in Coxiella burnetii infection

A Novel Pathway for Inducible Nitric-oxide Synthase Activation through Inflammasomes

Apoptosis-Associated Speck–like Protein Containing a Caspase Recruitment Domain Inflammasomes Mediate IL-1β Response and Host Resistance to Trypanosoma cruzi Infection

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