scholarly journals Acute inflammation, mediated by lung neutrophils, confers enhanced protection against Mycobacterium tuberculosis infection in mice

2021 ◽  
Author(s):  
Tucker J. Piergallini ◽  
Julia M. Scordo ◽  
Paula A. Pino ◽  
Jordi B. Torrelles ◽  
Joanne Turner
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Acute Inflammation ◽  
Mycobacterium Tuberculosis Infection ◽  
Positive Role ◽  
Innate Capacity ◽  
Time Of Infection ◽  
Lps Treatment ◽  
Partial Depletion

AbstractInflammation plays a crucial role in the control of Mycobacterium tuberculosis (M.tb) infection. In this study, we demonstrate that an inflammatory pulmonary environment at the time of infection mediated by liposaccharide (LPS) treatment in mice confers enhanced protection against M.tb for up to 6 months post infection. This transient protective inflammatory environment was associated with a neutrophil and monocyte/macrophage influx as well as increased inflammatory cytokines. In vitro infection of neutrophils from LPS treated mice demonstrated that LPS neutrophils exhibited increased recognition of M.tb, and had a greater innate capacity for killing M.tb. Finally, partial depletion of neutrophils in LPS treated mice showed an increase in M.tb burden, suggesting neutrophils conferred the enhanced protection observed in LPS treated mice. These results indicate a positive role of an inflammatory environment during initial M.tb infection, and suggests that acute inflammation at the time of M.tb infection can positively alter disease outcome.

scholarly journals Involvement of HECTD1 in LPS-induced astrocyte activation via σ-1R-JNK/p38-FOXJ2 axis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ying Tang ◽  
Mengchun Zhou ◽  
Rongrong Huang ◽  
Ling Shen ◽  
Li Yang ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Astrocyte Activation ◽  
Hect Domain ◽  
P38 Inhibitor ◽  
Ubiquitin Protein Ligase ◽  
Primary Mouse ◽  
Lps Treatment

Abstract Background Astrocytes participate in innate inflammatory responses within the mammalian central nervous system (CNS). HECT domain E3 ubiquitin protein ligase 1 (HECTD1) functions during microglial activation, suggesting a connection with neuroinflammation. However, the potential role of HECTD1 in astrocytes remains largely unknown. Results Here, we demonstrated that HECTD1 was upregulated in primary mouse astrocytes after 100 ng/ml lipopolysaccharide (LPS) treatment. Genetic knockdown of HECTD1 in vitro or astrocyte-specific knockdown of HECTD1 in vivo suppressed LPS-induced astrocyte activation, whereas overexpression of HECTD1 in vitro facilitated LPS-induced astrocyte activation. Mechanistically, we established that LPS activated σ-1R-JNK/p38 pathway, and σ-1R antagonist BD1047, JNK inhibitor SP600125, or p38 inhibitor SB203580 reversed LPS-induced expression of HECTD1, thus restored LPS-induced astrocyte activation. In addition, FOXJ2 functioned as a transcription factor of HECTD1, and pretreatment of primary mouse astrocytes with BD1047, SB203580, and SP600125 significantly inhibited LPS-mediated translocation of FOXJ2 into the nucleus. Conclusions Overall, our present findings suggest that HECTD1 participates in LPS-induced astrocyte activation by activation of σ-1R-JNK/p38-FOXJ2 pathway and provide a potential therapeutic strategy for neuroinflammation induced by LPS or any other neuroinflammatory disorders.

scholarly journals Obesity-Induced Dysbiosis Exacerbates IFN-γ Production and Pulmonary Inflammation in the Mycobacterium tuberculosis Infection

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1732
Author(s):  
Sandra Patricia Palma Albornoz ◽  
Thais Fernanda de Campos Fraga-Silva ◽  
Ana Flávia Gembre ◽  
Rômulo Silva de Oliveira ◽  
Fernanda Mesquita de Souza ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Gut Microbiota ◽  
Inflammatory Diseases ◽  
Pulmonary Inflammation ◽  
Host Susceptibility ◽  
Chronic Infections ◽  
Mycobacterium Tuberculosis Infection ◽  
Pulmonary Damage ◽  
Ifn Γ

The microbiota of the gut–lung axis affects local and far-reaching immune responses and might also trigger chronic and inflammatory diseases. We hypothesized that gut dysbiosis induced by obesity, which coexists in countries with a high tuberculosis burden, aggravates the host susceptibility and the pulmonary damage tolerance. To assess our hypothesis, we used a model of high-fat diet (HFD)-induced obesity, followed by infection of C57BL/6 mice with Mycobacterium tuberculosis. We showed that obesity increased the susceptibility, the pulmonary inflammation and IFN-γ levels in M. tuberculosis-infected mice. During the comorbidity obesity and tuberculosis, there is an increase of Bacteroidetes and Firmicutes in the lungs, and an increase of Firmicutes and butyrate in the feces. Depletion of gut microbiota by antibiotic treatment in the obese infected mice reduced the frequencies of CD4+IFN-γ+IL-17− cells and IFN-γ levels in the lungs, associated with an increase of Lactobacillus. Our findings reinforce the role of the gut–lung axis in chronic infections and suggest that the gut microbiota modulation may be a potential host-directed therapy as an adjuvant to treat TB in the context of IFN-γ-mediated immunopathology.

scholarly journals The Role of QuantiFERON-TB Gold Plus in Mycobacterium Tuberculosis Detection in a Severe HIV Immunocompromised Patient—Case Report

Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1523
Author(s):  
Florentina Dumitrescu ◽  
Cătălina-Gabriela Pisoschi ◽  
Vlad Pădureanu ◽  
Andreea Cristina Stoian ◽  
Livia Dragonu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immunocompromised Patient ◽  
Symptomatic Treatment ◽  
Pneumocystis Pneumonia ◽  
Hiv Positive ◽  
Patient Case ◽  
Mycobacterium Tuberculosis Infection ◽  
Antituberculosis Therapy ◽  
Antituberculosis Treatment

Tuberculosis (TB) is an important opportunistic infection in HIV-positive people. We are reporting a case of a 31-year-old HIV-infected patient who was hospitalized in July 2021 for dyspnea, cough with mucopurulent sputum and asthenia. He was confirmed to have Serratia liquefaciens pneumonia and acute respiratory failure. The evolution was unfavorable despite the antibiotic, pathogenic and symptomatic treatment. Because the patient had severe immunosuppression (CD4 count = 37 cell/mm3), we used QuantiFERON-TB Gold Plus for the detection of the Mycobacterium tuberculosis infection. The antituberculosis therapy was initiated, which resulted in a significant improvement of the general condition and the patient was discharged with the recommendation to continue antiretroviral therapy, antituberculosis treatment and Trimethoprim/Sulfamethoxazole—single tablet daily for the prophylaxis of Pneumocystis pneumonia.

scholarly journals The Mycobacterium tuberculosis sRNA F6 regulates expression of groEL/S

2020 ◽  
Author(s):  
Joanna Houghton ◽  
Angela Rodgers ◽  
Graham Rose ◽  
Kristine B. Arnvig
Keyword(s):  
Gene Expression ◽  
Mycobacterium Tuberculosis ◽  
Small Rnas ◽  
Transcriptional Control ◽  
Cold Shock ◽  
Control Of Gene Expression ◽  
Rna Biology ◽  
Mouse Model Of Infection

ABSTRACTAlmost 140 years after the identification of Mycobacterium tuberculosis as the etiological agent of tuberculosis, important aspects of its biology remain poorly described. Little is known about the role of post-transcriptional control of gene expression and RNA biology, including the role of most of the small RNAs (sRNAs) identified to date. We have carried out a detailed investigation of the M. tuberculosis sRNA, F6, and show it to be dependent on SigF for expression and significantly induced during in vitro starvation and in a mouse model of infection. However, we found no evidence of attenuation of a ΔF6 strain within the first 20 weeks of infection. A further exploration of F6 using in vitro models of infection suggests a role for F6 as a highly specific regulator of the heat shock repressor, HrcA. Our results point towards a role for F6 during periods of low metabolic activity similar to cold shock and associated with nutrient starvation such as that found in human granulomas in later stages of infection.

Rv2223c, an acid inducible carboxyl-esterase of Mycobacterium tuberculosis enhanced the growth and survival of Mycobacterium smegmatis

2019 ◽  
Vol 14 (16) ◽  
pp. 1397-1415
Author(s):  
Pratibha Maan ◽  
Jagdeep Kaur
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Smegmatis ◽  
Intracellular Survival ◽  
Growth And Survival ◽  
Enhanced Expression ◽  
Stress Environment ◽  
In Vitro Stress ◽  
Carboxyl Esterase

Aim: To elucidate the role of Rv2223c in Mycobacterium tuberculosis. Methods: Purified recombinant Rv2223c protein was characterized. Expression of rv2223c in the presence of different stress environment and subcellular localization were performed in M. tuberculosis H37Ra and Mycobacterium smegmatis ( MS_2223c). Effect of its overexpression on growth rate, infection and intracellular survival in THP-1/PBMC cells were studied. Results: rRv2223c demonstrated esterase activity with preference for pNP-octanoate and hydrolyzed trioctanoate to di- and mono-octanoate. Expression of rv2223c was upregulated in acidic and nutritive stress conditions. rRv2223c was identified in extracellular and cell wall fractions. MS_2223c exhibited enhanced growth, survival during in vitro stress, infection and intracellular survival. Conclusions: Rv2223c is a secretary, carboxyl-esterase, with enhanced expression under acidic and nutritive stress condition and might help in intracellular survival of bacteria.

IL-10 deficiency increases superoxide and endothelial dysfunction during inflammation

2000 ◽  
Vol 279 (4) ◽  
pp. H1555-H1562 ◽  
Author(s):  
Carol A. Gunnett ◽  
Donald D. Heistad ◽  
Daniel J. Berg ◽  
Frank M. Faraci
Keyword(s):  
Endothelial Function ◽  
Xanthine Oxidase ◽  
Carotid Arteries ◽  
Interleukin 10 ◽  
Vehicle Injection ◽  
Endothelium Dependent Relaxation ◽  
Deficient Mice ◽  
Lps Treatment

Little is known about the role of interleukin-10 (IL-10), an anti-inflammatory cytokine, in blood vessels. We used IL-10-deficient mice (IL-10 −/−) to examine the hypothesis that IL-10 protects endothelial function after lipopolysaccharide (LPS) treatment. The responses of carotid arteries were studied in vitro 6 h after injection of a relatively low dose of LPS (10 μg ip). In IL-10 −/− mice, the maximum relaxation to ACh (3 μM) was 56 ± 6% (means ± SE) after LPS injection and 84 ± 4% after vehicle injection ( P < 0.05). Thus endothelium-dependent relaxation was impaired in carotid arteries from IL-10 −/− mice after LPS injection. In contrast, this dose of LPS did not alter relaxation to ACh in vessels from wild-type (IL-10 +/+) mice. Relaxation to nitroprusside and papaverine was similar in arteries from both IL-10 −/− and IL-10 +/+ mice after vehicle or LPS injection. Because inflammation is associated with increased levels of reactive oxygen species, we also tested the hypothesis that superoxide contributes to the impairment of endothelial function by LPS in the absence of IL-10. Results using confocal microscopy and hydroethidine indicated that levels of superoxide are elevated in carotid arteries from IL-10 −/− mice compared with IL-10 +/+ mice after LPS injection. The impaired relaxation of arteries from IL-10 −/− mice after LPS injection was restored to normal by polyethylene glycol-suspended superoxide dismutase (50 U/ml) or allopurinol (1 mM), an inhibitor of xanthine oxidase. These data provide direct evidence that IL-10 protects endothelial function after an acute inflammatory stimulus by limiting local increases in superoxide. The source of superoxide in this model may be xanthine oxidase.

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