scholarly journals A MyD88-Deficient Mouse Model Reveals a Role for Nramp1 in Campylobacter jejuni Infection

2007 ◽  
Vol 75 (4) ◽  
pp. 1994-2003 ◽  
Author(s):  
Robert O. Watson ◽  
Veronica Novik ◽  
Dirk Hofreuter ◽  
María Lara-Tejero ◽  
Jorge E. Galán
Keyword(s):  
Campylobacter Jejuni ◽  
Virulence Genes ◽  
Potential Role ◽  
Bacterial Pathogen ◽  
Adaptor Protein ◽  
Myeloid Differentiation ◽  
Deficient Mouse ◽  
Immunocompetent Mice ◽  
Myeloid Differentiation Factor ◽  
Deficient Mice

ABSTRACT Campylobacter jejuni is a major worldwide cause of enteric illnesses. Adult immunocompetent mice are not susceptible to C. jejuni infection. However, we show here that mice deficient in the adaptor protein myeloid differentiation factor 88 (MyD88), which is required for signaling through most Toll-like receptors, can be stably colonized by C. jejuni but not by isogenic derivatives carrying mutations in known virulence genes. We also found that Nramp1 deficiency increases the mouse susceptibility to C. jejuni infection when administered systemically. These results indicate that MyD88-deficient mice could be a useful model to study C. jejuni colonization and reveal a potential role for Nramp1 in the control of this bacterial pathogen.

scholarly journals Innate immunity against Francisella tularensis is dependent on the ASC/caspase-1 axis

2005 ◽  
Vol 202 (8) ◽  
pp. 1043-1049 ◽  
Author(s):  
Sanjeev Mariathasan ◽  
David S. Weiss ◽  
Vishva M. Dixit ◽  
Denise M. Monack
Keyword(s):  
Francisella Tularensis ◽  
Bacterial Pathogen ◽  
Adaptor Protein ◽  
Innate Immune ◽  
Wild Type ◽  
Innate Defense ◽  
Caspase 1 ◽  
Host Cell Death ◽  
Host Defense Response ◽  
Deficient Mice

Francisella tularensis is a highly infectious gram-negative coccobacillus that causes the zoonosis tularemia. This bacterial pathogen causes a plague-like disease in humans after exposure to as few as 10 cells. Many of the mechanisms by which the innate immune system fights Francisella are unknown. Here we show that wild-type Francisella, which reach the cytosol, but not Francisella mutants that remain localized to the vacuole, induced a host defense response in macrophages, which is dependent on caspase-1 and the death-fold containing adaptor protein ASC. Caspase-1 and ASC signaling resulted in host cell death and the release of the proinflammatory cytokines interleukin (IL)-1β and IL-18. F. tularensis–infected caspase-1– and ASC-deficient mice showed markedly increased bacterial burdens and mortality as compared with wild-type mice, demonstrating a key role for caspase-1 and ASC in innate defense against infection by this pathogen.

scholarly journals Expression of human TLR4/myeloid differentiation factor 2 directs an early innate immune response associated with modest increases in bacterial burden during Coxiella burnetii infection

2019 ◽  
Vol 25 (7) ◽  
pp. 401-411
Author(s):  
Amanda Robison ◽  
Deann T Snyder ◽  
Kelly Christensen ◽  
Emily Kimmel ◽  
Adeline M Hajjar ◽  
...  
Keyword(s):  
Coxiella Burnetii ◽  
Hematopoietic Cells ◽  
Adaptor Protein ◽  
Myeloid Differentiation ◽  
Target Cells ◽  
Lung Pathology ◽  
Bacterial Burden ◽  
Wild Type ◽  
Differentiation Factor ◽  
Myeloid Differentiation Factor

Human TLR4 (hTLR4) and mouse TLR4 molecules respond differently to hypo-acylated LPS. The LPS of Coxiella burnetii is hypo-acylated and heavily glycosylated and causes a minimal response by human cells. Thus, we hypothesized that mice expressing hTLR4 molecules would be more susceptible to C. burnetii infection. Our results show that transgenic mice expressing hTLR4 and the human myeloid differentiation factor 2 (MD-2) adaptor protein (hTLR4/MD-2) respond similarly to wild type mice with respect to overall disease course. However, differences in bacterial burdens in tissues were noted, and lung pathology was increased in hTLR4/MD2 compared to wild type mice. Surprisingly, bone marrow chimera experiments indicated that hTLR4/MD-2 expression on non-hematopoietic cells, rather than the target cells for C. burnetii infection, accounted for increased bacterial burden. Early during infection, cytokines involved in myeloid cell recruitment were detected in the plasma of hTLR4/MD2 mice but not wild type mice. This restricted cytokine response was accompanied by neutrophil recruitment to the lung in hTLR4/MD2 mice. These data suggest that hTLR4/MD-2 alters early responses during C. burnetii infection. These early responses are precursors to later increased bacterial burdens and exacerbated pathology in the lung. Our data suggest an unexpected role for hTLR4/MD-2 in non-hematopoietic cells during C. burnetii infection.

scholarly journals MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18

2010 ◽  
Vol 207 (8) ◽  
pp. 1625-1636 ◽  
Author(s):  
Rosalba Salcedo ◽  
Andrea Worschech ◽  
Marco Cardone ◽  
Yava Jones ◽  
Zsofia Gyulai ◽  
...  
Keyword(s):  
Differential Susceptibility ◽  
Adaptor Protein ◽  
Protective Role ◽  
Dss Colitis ◽  
Expression Of Genes ◽  
Cancer Models ◽  
Genes Encoding ◽  
Myd88 Signaling ◽  
Myeloid Differentiation Factor ◽  
Deficient Mice

Signaling through the adaptor protein myeloid differentiation factor 88 (MyD88) promotes carcinogenesis in several cancer models. In contrast, MyD88 signaling has a protective role in the development of azoxymethane (AOM)/dextran sodium sulfate (DSS) colitis-associated cancer (CAC). The inability of Myd88−/− mice to heal ulcers generated upon injury creates an altered inflammatory environment that induces early alterations in expression of genes encoding proinflammatory factors, as well as pathways regulating cell proliferation, apoptosis, and DNA repair, resulting in a dramatic increase in adenoma formation and progression to infiltrating adenocarcinomas with frequent clonal mutations in the β-catenin gene. Others have reported that toll-like receptor (Tlr) 4–deficient mice have a similar susceptibility to colitis to Myd88-deficient mice but, unlike the latter, are resistant to CAC. We have observed that mice deficient for Tlr2 or Il1r do not show a differential susceptibility to colitis or CAC. However, upon AOM/DSS treatment Il18−/− and Il18r1−/− mice were more susceptible to colitis and polyp formation than wild-type mice, suggesting that the phenotype of Myd88−/− mice is, in part, a result of their inability to signal through the IL-18 receptor. This study revealed a previously unknown level of complexity surrounding MyD88 activities downstream of different receptors that impact tissue homeostasis and carcinogenesis.

scholarly journals Lethal Encephalitis in Myeloid Differentiation Factor 88-Deficient Mice Infected with Herpes Simplex Virus 1

2005 ◽  
Vol 166 (5) ◽  
pp. 1419-1426 ◽  
Author(s):  
Daniel S. Mansur ◽  
Erna G. Kroon ◽  
Maurício L. Nogueira ◽  
Rosa M.E. Arantes ◽  
Soraia C.O. Rodrigues ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Myeloid Differentiation ◽  
Herpes Simplex Virus 1 ◽  
Differentiation Factor ◽  
Myeloid Differentiation Factor 88 ◽  
Simplex Virus ◽  
Myeloid Differentiation Factor ◽  
Deficient Mice

Tanshinone IIA attenuates elastase-induced AAA in rats via inhibition of MyD88-dependent TLR-4 signaling

VASA ◽  
2014 ◽  
Vol 43 (1) ◽  
pp. 39-46 ◽  
Author(s):  
Tao Shang ◽  
Feng Ran ◽  
Qian Qiao ◽  
Zhao Liu ◽  
Chang-Jian Liu
Keyword(s):  
Nuclear Factor Κb ◽  
Tanshinone Iia ◽  
Myeloid Differentiation ◽  
Aortic Tissue ◽  
Toll Like Receptor ◽  
Sprague Dawley ◽  
Toll Like Receptor 4 ◽  
Tissue Samples ◽  
Myeloid Differentiation Factor ◽  
And Control

Background: The purpose of this study was to determine whether myeloid differentiation factor88-dependent Toll-Like Receptor-4 (TLR-4) signaling contributed to the inhibition of abdominal aortic aneurysm (AAA) by Tanshinone IIA (Tan IIA). Materials and methods: Male Sprague-Dawley rats (n = 12 / group) were randomly distributed into three groups: Tan IIA, control, and sham. The rats from Tan IIA and control groups under-went intra-aortic elastase perfusion to induce AAAs, and those in the sham group were perfused with saline. Only the Tan IIA group received Tan IIA (2 mg / rat / d). Aortic tissue samples were harvested at 24 d after perfusion and evaluated using reverse transcriptase-polymerase chain reaction, Western blot, immunohistochemistry and immunofluorescence. Results: The over-expression of Toll-Like Receptor-4 (TLR-4), Myeloid Differentiation factor 88 (MyD88), Phosphorylated Nuclear Factor κB (pNF-κB) and Phosphorylated IκBα (pIκBα) induced by elastase perfusion were significantly decreased by Tan IIA treatment. Conclusions: Tan IIA attenuates elastase-induced AAA in rats possibly via the inhibition of MyD88-dependent TLR-4 signaling, which may be one potential explanation of why Tan IIA inhibits AAA development through multiple effects.

Chelidonine Attenuates Sepsis-Induced Acute Lung Injury via Suppressing Toll-like Receptor 4/Myeloid Differentiation Factor 88/Nuclear Factor-॔B Signaling Pathway in Newborn Mice

2020 ◽  
Vol 19 (1) ◽  
pp. 120-126
Author(s):  
Ayinuerguli Adili ◽  
Adilijiang Kari ◽  
Chuanlong Song ◽  
Abulaiti Abuduhaer
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Nuclear Factor Kappa B ◽  
Myeloid Differentiation ◽  
Nuclear Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Inflammatory Infiltration ◽  
Newborn Mice ◽  
Myeloid Differentiation Factor

We have examined the mechanism underlying amelioration of sepsis-induced acute lung injury by chelidonine in newborn mice. To this end, a sepsis model was established using cecal ligation and puncture in newborn mice. The sepsis-induced acute lung injury was associated with an increased inflammatory infiltration and pulmonary congestion, as well as abnormal alveolar morphology. The lung injury-associated increased tumor necrosis factor-α and interleukin-1β in bronchoalveolar lavage fluid and lung, the markers of inflammatory infiltration and pulmonary congestion, diminished by chelidonine treatment. Chelidonine administration also downregulated protein levels of toll-like receptor 4, myeloid differentiation factor 88, phosphorylated nuclear factor-kappa B, and nuclear factor-kappa B that are elevated in response to sepsis. In conclusion, chelidonine provides a potential therapeutic strategy for newborn mice with acute lung injury.

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