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 PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques

2021 ◽  
Vol 6 (55) ◽  
pp. eabf3861
Author(s):  
Keith D. Kauffman ◽  
Shunsuke Sakai ◽  
Nickiana E. Lora ◽  
Sivaranjani Namasivayam ◽  
Paul J. Baker ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Cell Function ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Imaging Studies ◽  
Chronic Infections ◽  
Mycobacterium Tuberculosis Infection ◽  
Cell Responses

Boosting immune cell function by targeting the coinhibitory receptor PD-1 may have applications in the treatment of chronic infections. Here, we examine the role of PD-1 during Mycobacterium tuberculosis (Mtb) infection of rhesus macaques. Animals treated with anti–PD-1 monoclonal antibody developed worse disease and higher granuloma bacterial loads compared with isotype control–treated monkeys. PD-1 blockade increased the number and functionality of granuloma Mtb-specific CD8 T cells. In contrast, Mtb-specific CD4 T cells in anti–PD-1–treated macaques were not increased in number or function in granulomas, expressed increased levels of CTLA-4, and exhibited reduced intralesional trafficking in live imaging studies. In granulomas of anti–PD-1–treated animals, multiple proinflammatory cytokines were elevated, and more cytokines correlated with bacterial loads, leading to the identification of a role for caspase 1 in the exacerbation of tuberculosis after PD-1 blockade. Last, increased Mtb bacterial loads after PD-1 blockade were found to associate with the composition of the intestinal microbiota before infection in individual macaques. Therefore, PD-1–mediated coinhibition is required for control of Mtb infection in macaques, perhaps because of its role in dampening detrimental inflammation and allowing for normal CD4 T cell responses.

scholarly journals PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques

2020 ◽  
Author(s):  
Keith D Kauffman ◽  
Shunsuke Sakai ◽  
Nickiana E Lora ◽  
Sivaranjani Namasivayam ◽  
Paul J Baker ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Cell Function ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Chronic Infections ◽  
Mycobacterium Tuberculosis Infection ◽  
Cell Responses ◽  
Pro Inflammatory Cytokines

ABSTRACTBoosting immune cell function by targeting the co-inhibitory receptor PD-1 may have applications in the treatment of chronic infections. Here we examine the role of PD-1 during Mycobacterium tuberculosis (Mtb) infection of rhesus macaques. Animals treated with αPD-1 mAb developed worse disease and higher granuloma bacterial loads compared to isotype control treated monkeys. PD-1 blockade increased the number and functionality of granuloma Mtb-specific CD8 T cells. In contrast, Mtb-specific CD4 T cells in αPD-1 treated macaques were not increased in number or function in granulomas, upregulated high levels of CTLA-4 and exhibited reduced intralesional trafficking in live imaging studies. In granulomas of αPD-1 treated animals, multiple pro-inflammatory cytokines were elevated, and more cytokines correlated with bacterial loads, leading to the identification of a role for caspase 1 in the exacerbation of tuberculosis after PD-1 blockade. Lastly, increased Mtb bacterial loads after PD-1 blockade were found to associate with the composition of the intestinal microbiota prior to infection in individual macaques. Therefore, PD-1-mediated co-inhibition is required for control of Mtb infection in macaques, perhaps due to its role in dampening detrimental inflammation as well as allowing for normal CD4 T cell responses.

THE INTESTINAL COMMENSAL, Bacteroides fragilis , MODULATES HOST RESPONSES TO VIRAL INFECTION AND THERAPY: LESSONS FOR EXPLORATION DURING Mycobacterium tuberculosis INFECTION

2021 ◽  
Author(s):  
Osagie A Eribo ◽  
Nelita du Plessis ◽  
Novel N Chegou
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Gut Microbiota ◽  
Bacterial Infections ◽  
Capsular Polysaccharide ◽  
Viral Infections ◽  
Respiratory Infections ◽  
Pulmonary Inflammation ◽  
Bacteroides Fragilis ◽  
Host Responses ◽  
Mycobacterium Tuberculosis Infection

The gut microbiota has emerged as a critical player in host health. Bacteroides fragilis is a prominent member of the gut microbiota within the phyla Bacteroidetes. This commensal bacterium produces unique capsular polysaccharides processed by antigen-presenting cells and activates CD4 + T cells to secrete inflammatory cytokines. Indeed, due to their immunomodulatory functions, B. fragilis and its capsular polysaccharide-A (PSA) are arguably the most explored single commensal microbiota/symbiotic factor. B. fragilis / PSA has been shown to protect against colitis, encephalomyelitis, colorectal cancer, pulmonary inflammation, and asthma. Here, we review (1) recent data on the immunomodulatory role of B. fragilis /PSA during viral infections and therapy, (2) B. fragilis PSA’s dual ability to mediate pro-and anti-inflammatory processes, and the potential for exploring this unique characteristic during intracellular bacterial infections such as with Mycobacterium tuberculosis (3) discuss the protective roles of single commensal-derived probiotic species including B. fragilis in lung inflammation and respiratory infections that may provide essential cues for possible exploration of microbiota based/augmented therapies in tuberculosis (TB). Available data on the relationship between B. fragilis / PSA, the immune system, and disease suggest clinical relevance for developing B. fragilis into a next-generation probiotic or, possibly, the engineering of PSA into a potent carbohydrate-based vaccine.

scholarly journals Cytokine Biosignature of Active and Latent Mycobacterium Tuberculosis Infection in Children

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 517
Author(s):  
Magdalena Druszczynska ◽  
Michal Seweryn ◽  
Sebastian Wawrocki ◽  
Magdalena Kowalewska-Pietrzak ◽  
Anna Pankowska ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Inflammatory Mediators ◽  
Latent Tuberculosis ◽  
Serum Levels ◽  
Diagnostic Tools ◽  
Mycobacterium Tuberculosis Infection ◽  
Only Children ◽  
Latent Tb ◽  
Ifn Γ ◽  
Multiplex Bead

None of the currently used diagnostic tools are efficient enough in diagnosing Mycobacterium tuberculosis (M.tb) infection in children. The study was aimed to identify cytokine biosignatures characterizing active and latent tuberculosis (TB) in children. Using a multiplex bead-based technology, we analyzed the levels of 53 Th17-related cytokines and inflammatory mediators in sera from 216 BCG-vaccinated children diagnosed with active TB (TB) or latent TB (LTBI) as well as uninfected controls (HC). Children with active TB, compared to HC children, showed reduced serum levels of IL-17A, MMP-2, OPN, PTX-3, and markedly elevated concentrations of APRIL/TNFSF13. IL-21, sCD40L, MMP-2, and IL-8 were significantly differentially expressed in the comparisons between groups: (1) HC versus TB and LTBI (jointly), and (2) TB versus LTBI. The panel consisting of APRIL/TNFSF13, sCD30/TNFRSF8, IFN-α2, IFN-γ, IL-2, sIL-6Rα, IL-8, IL-11, IL-29/IFN-λ1, LIGHT/TNFSF14, MMP-1, MMP-2, MMP-3, osteocalcin, osteopontin, TSLP, and TWEAK/TNFSF12 possessed a discriminatory potential for the differentiation between TB and LTBI children. Serum-based host biosignatures carry the potential to aid the diagnosis of childhood M.tb infections. The proposed panels of markers allow distinguishing not only children infected with M.tb from uninfected individuals but also children with active TB from those with latent TB.

scholarly journals Neither Primary nor Memory Immunity to Mycobacterium tuberculosis Infection Is Compromised in Mice with Chronic Enteric Helminth Infection

2015 ◽  
Vol 83 (3) ◽  
pp. 1217-1223 ◽  
Author(s):  
Wasiulla Rafi ◽  
Kamlesh Bhatt ◽  
William C. Gause ◽  
Padmini Salgame
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Regulatory Cells ◽  
Helminth Infection ◽  
Treg Cells ◽  
Helminth Species ◽  
Nippostrongylus Brasiliensis ◽  
T Regulatory Cell ◽  
Chronic Infections ◽  
Mycobacterium Tuberculosis Infection ◽  
Content Type

Previously we had reported thatNippostrongylus brasiliensis, a helminth with a lung migratory phase, affected host resistance againstMycobacterium tuberculosisinfection through the induction of alternatively activated (M2) macrophages. Several helminth species do not have an obligatory lung migratory phase but establish chronic infections in the host that include potent immune downregulatory effects, in part mediated through induction of a FoxP3+T regulatory cell (Treg) response. Treg cells exhibit duality in their functions in host defense againstM. tuberculosisinfection since their depletion leads to enhanced priming of T cells in the lymph nodes and attendant improved control ofM. tuberculosisinfection, while their presence in the lung granuloma protects against excessive inflammation.Heligmosomoides polygyrusis a strictly murine enteric nematode that induces a strong FoxP3 Treg response in the host. Therefore, in this study we investigated whether host immunity toM. tuberculosisinfection would be modulated in mice with chronicH. polygyrusinfection. We report that neither primary nor memory immunity conferred byMycobacterium bovisBCG vaccination was affected in mice with chronic enteric helminth infection, despite a systemic increase in FoxP3+T regulatory cells. The findings indicate that anti-M. tuberculosisimmunity is not similarly affected by all helminth species and highlight the need to consider this inequality in human coinfection studies.

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 Evaluation of a lateral flow assay for rapid and simple detection of IFN-γ for the diagnosis of Mycobacterium tuberculosis infection

2020 ◽  
Author(s):  
Jeong-Ran Kim ◽  
Hae Yeong Kang ◽  
Su-Bin Seong ◽  
Nari Kim ◽  
Tae Sun Shim ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Lateral Flow ◽  
Lateral Flow Assay ◽  
Tuberculosis Infection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mycobacterium Tuberculosis Infection ◽  
Blood Samples ◽  
Simple Detection ◽  
Laboratory Workers ◽  
Ifn Γ

Abstract Background: Interferon-gamma (IFN-γ) release assays (IGRAs) are useful for the diagnosis of Mycobacterium tuberculosis infection. Current IGRAs use either enzyme-linked immunosorbent assay (ELISA) or enzyme-linked immunospot assay, which require complex procedures and techniques to determine IFN-γ secretion. We aimed to compare the usefulness of the easy-to-use lateral flow assay (LFA) with that of the QuantiFERON-TB Gold In-Tube (QFT-GIT) or QuantiFERON-TB Gold Plus (QFT-plus) ELISAs for detecting IFN-γ, produced by the blood T cells stimulated by tuberculosis (TB) antigen. Methods: Following informed consent, 176 participants, including health care workers such as TB laboratory workers and radiologists, were enrolled for the study from June 2017 to June 2018. Blood samples were collected and tested using QFT-GIT and QFT-plus. The secreted IFN-γ was quantified by LFA, which took approximately 15 min, and ELISA, which took approximately 3 h. Results: A total of 176 blood samples were screened. The positive rates of QFT-GIT and QFT-plus were 34.1% and 37.5%, respectively. Overall agreement between QFT-GIT and QFT-plus was 93.1% ( κ = 0.86). The positive rates of LFA with QFT-GIT tube and QFT-plus tube were 25.6% and 31.3%, respectively, overall agreement of LFA being 90.3% ( κ = 0.78) and 89.2% ( κ = 0.77), respectively, compared to the QFT-GIT and QFT-plus ELISA. Conclusion: The ability of LFA to measure IFN-γ was similar to that of ELISA. The current findings suggested that the new LFA could be more conveniently utilized for diagnosing TB infection.

scholarly journals Effect of Thymoquinone on Th1 and Th2 Balance in Rats Infected with Mycobacterium tuberculosis

2021 ◽  
Vol 9 (A) ◽  
pp. 688-692
Author(s):  
Ery Olivianto ◽  
Agustina Tri Endharti ◽  
H.M.S. Chandra Kusuma ◽  
Sanarto Santoso ◽  
Kusworini Handono
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Nigella Sativa ◽  
Tuberculosis Infection ◽  
Mycobacterium Tuberculosis Infection ◽  
Ifn Γ ◽  
Th2 Differentiation ◽  
Different Doses ◽  
Strain H37rv ◽  
Mycobacterium Tuberculosis Strain ◽  
Th1 And Th2

Thymoquinone is an active compound in Nigella sativa which has potential immunomodulatory effect. Mycobacterium tuberculosis could alter the Th1 and Th2 balance by stimulating phagocyte IL-1β production, and subsequent Th2 differentiation. We aim to evaluate the effect of thymoquinone (TQ) in restore the Th1 and Th2 balance in Mycobacterium tuberculosis infection. Four groups of rats were infected with virulent Mycobacterium tuberculosis strain H37Rv. Thymoquinone at different doses was given to three groups, and one group left without treatment. Additional one group was either infected or treated with TQ. We measure IL-1β, IL-4 and IFN-γ levels using ELISA 14 days after TQ treatment. We found there were increased IL-1β, IL-4 and IFN-γ level after Mycobacterium tuberculosis infection, but we observe no significant effect of TQ treatment to Th1 and Th2 balance.  We conclude that TQ could not restore Th1 and Th2 balance in rats infected with Mycobacterium tuberculosis.

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