Faculty Opinions recommendation of S100A8/A9 regulates CD11b expression and neutrophil recruitment during chronic tuberculosis.
Year: 2020
Type: peer-review
Abstract: Neutrophil accumulation is associated with lung pathology during active tuberculosis (ATB). However, the molecular mechanism or mechanisms by which neutrophils accumulate in the lung and contribute to TB immunopathology are not fully delineated. Using the well-established mouse model of TB, our new data provide evidence that the alarmin S100A8/A9 mediates neutrophil accumulation during progression to chronic TB. Depletion of neutrophils or S100A8/A9 deficiency resulted in improved Mycobacterium tuberculosis (Mtb) control during chronic but not acute TB. Mechanistically, we demonstrate that, following Mtb infection, S100A8/A9 expression is required for upregulation of the integrin molecule CD11b specifically on neutrophils, mediating their accumulation during chronic TB disease. These findings are further substantiated by increased expression of S100A8 and S100A9 mRNA in whole blood in human TB progressors when compared with nonprogressors and rapidly decreased S100A8/A9 protein levels in the serum upon TB treatment. Furthermore, we demonstrate that S100A8/A9 serum levels along with chemokines are useful in distinguishing between ATB and asymptomatic Mtb-infected latent individuals. Thus, our results support targeting S100A8/A9 pathways as host-directed therapy for TB. PMID: 32134742 Funding information This work was supported by: NIGMS NIH HHS, United States Grant ID: R25 GM103757 NIAID NIH HHS, United States Grant ID: R01 AI111914
Authors: Eric Skaar, Lauren Palmer
Institution: Vanderbilt University Medical Center
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Washington University in St. Louis, Deutsche Forschungsgemeinschaft, Westfälische Wilhelms-Universität Münster, Instituto Mexicano del Seguro Social, University of Cape Town, Instituto de Seguriidad y Servicios Sociales de los Trabadores del Estado, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases
Awards: G150867648, G171904639, G2646711713, G2860138977, G3161234918, G3237399562, G4304959240, G4922938341, G6844960556, COMMON IMMUNE CORRELATES OF RISK OF TB DISEASE IN ANIMAL MODELS AND HUMANS, Role of Inducible Bronchus Associated Lymphoid Tissue in Latent Tuberculosis, Role of IL-17 in Protective Vaccine-induced Immune Responses Against Tuberculosis, Principles in Pulmonary Research
OpenAlex ID: W4231294699