Alcohol enhances type 1 interferon-α production and mortality in young mice infected with Mycobacterium tuberculosis

Tripathi, Deepak; Welch, Elwyn; Cheekatla, Satyanarayana; Radhakrishnan, Rajesh; Venkatasubramanian, Sambasivan; Paidipally, Padmaja; Van, Abhinav; Samten, Buka; Devalraju, Kamakshi Prudhula; Neela, Venkata Sanjeev Kumar; Valluri, Vijaya Lakshmi; Mason, Carol M.; Nelson, Steve; Vankayalapati, Ramakrishna

doi:10.1371/journal.ppat.1007174

Cited by 14 publications

(11 citation statements)

References 57 publications

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“…Upregulation of these significant Type I IFN signaling genes suggest that in a model of self-limited clinical disease in macaques, Type I IFN induction may be differentially regulated by age-associated factors. Age-specific regulation of this pathway has been demonstrated in the murine model of TB 70 . There is also a well-documented relationship between Notch signaling and viral infections.…”

Section: Discussionmentioning

confidence: 96%

IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection

et al. 2021

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SARS-CoV-2 virus has infected more than 92 million people worldwide resulting in the Coronavirus disease 2019 (COVID-19). Using a rhesus macaque model of SARS-CoV-2 infection, we have characterized the transcriptional signatures induced in the lungs of juvenile and old macaques following infection. Genes associated with Interferon (IFN) signaling, neutrophil degranulation and innate immune pathways are significantly induced in macaque infected lungs, while pathways associated with collagen formation are downregulated, as also seen in lungs of macaques with tuberculosis. In COVID-19, increasing age is a significant risk factor for poor prognosis and increased mortality. Type I IFN and Notch signaling pathways are significantly upregulated in lungs of juvenile infected macaques when compared with old infected macaques. These results are corroborated with increased peripheral neutrophil counts and neutrophil lymphocyte ratio in older individuals with COVID-19 disease. Together, our transcriptomic studies have delineated disease pathways that improve our understanding of the immunopathogenesis of COVID-19.

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Section: Discussionmentioning

confidence: 96%

IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection

et al. 2021

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“…A recently published study on a mouse model to determine the effects of chronic alcohol consumption on immune responses during M. tuberculosis infection demonstrated that alcohol enhanced IFN-α production by CD11b+Ly6G+ cells in the lungs of young Mtb-infected mice, which led to macrophage necroptosis and increased mortality. Their findings also suggest that young alcoholic individuals with latent tuberculosis have a higher risk of developing active tuberculosis infection 25 . The prevalence of alcoholism among patients with tuberculosis is 8%-10%, and there is a significantly higher incidence of tuberculosis recurrence among alcoholics.…”

Section: Discussionmentioning

confidence: 97%

The Role of Cigarette Smoking and Alcohol Consumption in Pulmonary Tuberculosis Development and Recurrence

Lampalo

Jukić

Bingulac-Popović

et al. 2019

ACC

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During a two-year period (2001-2003), 464 patients were treated for tuberculosis at Jordanovac Department for Lung Diseases in Croatia. Besides pulmonary tuberculosis in 97.7% of patients, patients were also treated for tuberculous pleurisy (0.9%), tuberculous laryngitis (0.6%), tuberculous meningitis (0.2%), tuberculous pericarditis (0.2%) and urogenital tuberculosis (0.4%). Out of the total number of patients, 57.3% declared themselves to be active smokers (men were predominant and made up to 80.8%) and 20.9% to be active alcohol consumers. Both risk factors, i.e. smoking and alcohol consumption, were present in 15.1% of all patients. The most common comorbidities were diabetes mellitus (30.4%), cardiac diseases (11.2%) and chronic obstructive pulmonary disease (8.0%). Lung carcinoma was the most common malignant disease (n=51), with Mycobacterium tuberculosis isolated in 33% of them. Seventy-two of 464 (15.5%) patients had recurrences of tuberculosis. Of these, 30.5% had one of the risk factors (20.8% were smokers and 9.7% consumed alcohol), while 32.5% of patients had both risk factors. In conclusion, cigarette smoking was proved to be the most significant risk factor for development of pulmonary tuberculosis and its recurrence.

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“…Up-regulation of these significant Type I IFN signaling genes suggest that in a model of self-limited clinical disease in macaques, Type I IFN induction may be differentially regulated by age-associated factors. Age-specific regulation of this pathway has been demonstrated in the murine model of TB( 72 ). There is also a well-documented relationship between Notch signaling and viral infections.…”

Section: Discussionmentioning

confidence: 99%

IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection

Rosa

Ahmed

Singh

et al. 2020

Preprint

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The novel virus SARS-CoV-2 has infected more than 14 million people worldwide resulting in the Coronavirus disease 2019 (COVID-19). Limited information on the underlying immune mechanisms that drive disease or protection during COVID-19 severely hamper development of therapeutics and vaccines. Thus, the establishment of relevant animal models that mimic the pathobiology of the disease is urgent. Rhesus macaques infected with SARS-CoV-2 exhibit disease pathobiology similar to human COVID-19, thus serving as a relevant animal model. In the current study, we have characterized the transcriptional signatures induced in the lungs of juvenile and old rhesus macaques following SARS-CoV-2 infection. We show that genes associated with Interferon (IFN) signaling, neutrophil degranulation and innate immune pathways are significantly induced in macaque infected lungs, while pathways associated with collagen formation are downregulated. In COVID-19, increasing age is a significant risk factor for poor prognosis and increased mortality. We demonstrate that Type I IFN and Notch signaling pathways are significantly upregulated in lungs of juvenile infected macaques when compared with old infected macaques. These results are corroborated with increased peripheral neutrophil counts and neutrophil lymphocyte ratio in older individuals with COVID-19 disease. In contrast, pathways involving VEGF are downregulated in lungs of old infected macaques. Using samples from humans with SARS-CoV-2 infection and COVID-19, we validate a subset of our findings. Finally, neutrophil degranulation, innate immune system and IFN gamma signaling pathways are upregulated in both tuberculosis and COVID-19, two pulmonary diseases where neutrophils are associated with increased severity. Together, our transcriptomic studies have delineated disease pathways to improve our understanding of the immunopathogenesis of COVID-19 to facilitate the design of new therapeutics for COVID-19.

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Alcohol enhances type 1 interferon-α production and mortality in young mice infected with Mycobacterium tuberculosis

Cited by 14 publications

References 57 publications

IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection

IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection

The Role of Cigarette Smoking and Alcohol Consumption in Pulmonary Tuberculosis Development and Recurrence

IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection

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