Coxiella burnetii Avirulent Nine Mile Phase II Induces Caspase-1-Dependent Pyroptosis in Murine Peritoneal B1a B Cells

Schoenlaub, Laura; Cherla, Rama P.; Zhang, Yan; Zhang, Guoquan

doi:10.1128/iai.00694-16

Cited by 17 publications

(18 citation statements)

References 66 publications

(75 reference statements)

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“…In contrast, our recent studies found that NMII can induce apoptosis in undifferentiated THP-1 cells through a caspase-3-independent pathway (22). We also found that NMII-infected murine peritoneal B1a cells undergo caspase-1-dependent pyroptosis through activation of Toll-like receptor 2 and NLRP3 signaling pathways (23). However, it remains unclear whether C. burnetii can modulate neutrophil apoptosis.…”

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confidence: 56%

Coxiella burnetii Inhibits Neutrophil Apoptosis by Exploiting Survival Pathways and Antiapoptotic Protein Mcl-1

et al. 2018

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Our previous study demonstrated that neutrophils play an important role in host defense against infection in mice. In this study, avirulent strain Nine Mile phase II (NMII) was used to examine if can modulate mouse bone marrow-derived neutrophil apoptosis. The results indicated that NMII can inhibit neutrophil apoptosis. Western blotting demonstrated that caspase-3 cleavage was decreased in NMII-infected neutrophils, while phosphorylated mitogen-activated protein kinase (MAPK) p38 and extracellular signal-regulated kinase 1 (Erk1) were increased. Additionally, p38, Erk1/2, phosphoinositide 3-kinase (PI3K), or NF-κB inhibitors reduced the ability of NMII to inhibit neutrophil apoptosis. These results suggest that NMII-mediated inhibition of neutrophil apoptosis depends on its ability to activate neutrophil MAPK pathways. Antiapoptotic protein myeloid cell leukemia-1 (Mcl-1) was significantly increased in NMII-infected neutrophils, and an Mcl-1 inhibitor significantly reduced the ability of NMII to inhibit neutrophil apoptosis. Mcl-1 protein stability was enhanced by phosphorylation at Thr-163 by Erk, and the protein levels were regulated by p38, Erk, PI3K, and NF-κB. Furthermore, the observation that a type IV secretion system (T4SS)-deficient mutant showed a significantly reduced ability to inhibit neutrophil apoptosis compared to wild-type (WT) NMII suggests that T4SS-secreted factors may be involved in NMII-induced inhibition of neutrophil apoptosis. Collectively, these results demonstrate that NMII inhibits neutrophil apoptosis through inhibition of caspase-3 cleavage and activation of MAPK survival pathways with subsequent expression and stabilization of antiapoptotic protein Mcl-1, a process that may partially require the T4SS.

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confidence: 56%

Coxiella burnetii Inhibits Neutrophil Apoptosis by Exploiting Survival Pathways and Antiapoptotic Protein Mcl-1

et al. 2018

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“…In the present study, results showed that B-1 and B-2 cells deficiency in XID mice together with cyclophosphamide treatment caused a more severe and spread encephalitozoonosis, which was similar the described to SCID and nude mice [28]. B-1 cells have phagocytic and microbicide capabilities [29] and are considered very important in the defense against Coxiella burnetti , by its ability to produce antibodies, cytokines and promote phagocytosis [30]. The lack of B cells increased the susceptibility of CBA/XID to Cryptococcus neoformans disseminated fungal disease [31].…”

Section: Discussionsupporting

confidence: 68%

Cyclophosphamide immunosuppressed Xid mice model clarify the protective role of B cells in experimental encephalitozoonosis

Crs

et al. 2018

Preprint

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21Encephalitozoon cuniculi is an intracellular pathogen that stablishes a balanced relationship 22 with immunocompetent individuals, which is dependent of T lymphocytes activity. We 23 previously showed X-linked immunodeficiency (XID -B cell deficient) mice are more 24 susceptible to encephalitozoonosis and B-1 cells presence influences in the immune response. 25 Because XID mice are deficient both in B-1 and B-2 cells, here we investigate the role of these 26 cells against E. cuniculi infection using cyclophosphamide (Cy) immunosuppressed murine 27 model to exacerbate the infection. XID mice presented lethargy and severe symptoms, 28 associated with encephalitozoonosis and there was an increase in the peritoneal populations of 29 CD8 + and CD4 + T lymphocytes and macrophages and also in the proinflammatory cytokines 30 IFN-γ, TNF-α and IL-6. In BALB/c mice, no clinical signs were observed and there was an 31 increase of T lymphocytes and macrophages in the spleen, showing an effective immune 32 response. B-2 cells transfer to XID mice resulted in reduction of symptoms and lesion area with 33 increase of B-2 and CD4 + T populations in the spleen. B-1 cells transfer increased the peritoneal 34 populations of B-2 cells and macrophages and also reduced the symptoms. Therefore, the 35 immunodeficiency of B cells associated to Cy immunosuppression condition leads to 36 disseminated and severe encephalitozoonosis in XID mice with absence of splenic immune 37 response and ineffective local immune response, evidencing the B-1 and B-2 cells role against 38 microsporidiosis.39 40 lymphocytes 42 43 3 44 Author summary 45 46 The adaptive immune response plays a key role against Encephalitozoon cuniculi, an 47 opportunistic fungus for T cells immunodeficient patients. The role of B cells and antibody play 48 in natural resistance to Encephalitozoon cuniculi remains unresolved. Previously, we 49 demonstrated that B-1 deficient mice (XID), an important component of innate immunity, were 50 more susceptible to encephalitozoonosis, despite the increase in the number of CD4 + and CD8 + 51 T lymphocytes. In order to better understand the role of B-1 and B-2 cells and the relationship 52 with the other cells of the immune response in encephalitozoonosis, we infected with E. cuniculi 53 in cyclophosphamide immunosuppressed mice. Here we demonstrate that infected XID mice 54 showed reduction of T cells and macrophages and increase of proinflammatory cytokines 55 associated with disseminated and severe encephalitozoonosis with presence of abdominal 56 effusion and lesions in multiple organs. This pattern of infection observed in mice with genetic 57 deficiency in T cells, so we suggest that the absence of B-1 cells affects the cytotoxic capacity 58 of these lymphocytes. When we transfer B-2 cells to XID mice, the lesion areas caused by the 59 fungus, the populations of T lymphocytes in the peritoneum and the proinflammatory cytokines 60 decrease, indicating a better resolution of the infection. We speculate that B-1 and B-2 cells...

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“…Pyroptosis is characterized by rapid plasma membrane rupture and the release of proinflammatory intracellular contents and is morphologically and mechanistically distinct from other forms of cell death. [33][34][35][36][37] Several studies have indicated that pyroptosis contributes to infectious diseases, nervous system disorders, and atherosclerosis. [38][39][40] Pyroptosis is sometimes followed by the induction of inflammasome formation, which is also pathogenic for the development of renal tissue damages in IR injuries.…”

Section: The Effects Of Foxo3 Knockdown On B-ohb Mediated Anti-pyroptmentioning

confidence: 99%

β-hydroxybutyrate attenuates renal ischemia-reperfusion injury through its anti-pyroptotic effects

Tajima

Yoshifuji

Matsui

et al. 2019

Kidney International

113

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Ketone bodies including b-hydroxybutyrate (b-OHB) have been shown to protect against ischemic tissue injury when present at low concentrations. We evaluated the impact of b-OHB on renal ischemia/reperfusion injury (IRI). Mice were treated with a continuous infusion of b-OHB using an osmotic mini-pump before and after IRI. We also tested the effects of increasing endogenous serum b-OHB levels by fasting. Renal IRI was attenuated by b-OHB treatment compared to saline control, with similar results in the fasting condition. b-OHB treatment reduced the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells and increased expression of forkhead transcription factor O3 (FOXO3), an upstream regulator of pyroptosis. Although b-OHB treatment did not impact markers of apoptosis, it decreased the expression of caspase-1 and proinflammatory cytokines, indicating that b-OHB blocked pyroptosis. In a human proximal tubular cell line exposed to hypoxia and reoxygenation, b-OHB reduced cell death in a FOXO3-dependent fashion. Histone acetylation was decreased in kidneys exposed to IRI and in proximal tubular cells exposed to hypoxia and reoxygenation, and this effect was ameliorated by b-OHB through the inactivation of histone deacetylases. In vitro, b-OHB treatment restored histone acetylation at the FOXO3 promoter. Consistent with epigenetic molecular effects, the renoprotective effects of b-OHB were still observed when the continuous infusion was stopped at the time of IRI. Thus, b-OHB attenuates renal IRI through anti-pyroptotic effects, likely mediated by an epigenetic effect on FOXO3 expression.

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Coxiella burnetii Avirulent Nine Mile Phase II Induces Caspase-1-Dependent Pyroptosis in Murine Peritoneal B1a B Cells

Cited by 17 publications

References 66 publications

Coxiella burnetii Inhibits Neutrophil Apoptosis by Exploiting Survival Pathways and Antiapoptotic Protein Mcl-1

Coxiella burnetii Inhibits Neutrophil Apoptosis by Exploiting Survival Pathways and Antiapoptotic Protein Mcl-1

Cyclophosphamide immunosuppressed Xid mice model clarify the protective role of B cells in experimental encephalitozoonosis

β-hydroxybutyrate attenuates renal ischemia-reperfusion injury through its anti-pyroptotic effects

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