Bruno B. Andrade, Artur T.L. Queiroz. Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Salvador, BA, Brasil.Andrea C. Bohrer (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Inflammation and Innate Immunity Unit. Bethesda, MD, United States of America.); Ehydel Castro (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Inflammation and Innate Immunity Unit. Bethesda, MD, United States of America.); Zhidong Hu (Fudan University. Shanghai Public Health Clinical Center. Department of Scientific Research. Shanghai, China / Fudan University. Shanghai Emerging and Re-emerging Infectious Disease Institute. Tuberculosis Center. Shanghai, China.); Artur T. L. Queiroz (The KAB Group / Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.); Claire E. Tocheny (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Inflammation and Innate Immunity Unit. Bethesda, MD, United States of America.); Maike Assmann (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Inflammation and Innate Immunity Unit. Bethesda, MD, United States of America.); Shunsuke Sakai (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. T Lymphocyte Biology Section. Bethesda, MD, United States of America.); Christine Nelson (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. T Lymphocyte Biology Section. Bethesda, MD, United States of America.); Paul J. Baker (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Inflammation and Innate Immunity Unit. Bethesda, MD, United States of America.); Hui Ma (Fudan University. Shanghai Public Health Clinical Center. Department of Scientific Research. Shanghai, China / Fudan University. Shanghai Emerging and Re-emerging Infectious Disease Institute. Tuberculosis Center. Shanghai, China.); Lin Wang (Fudan University. Shanghai Emerging and Re-emerging Infectious Disease Institute. Tuberculosis Center. Shanghai, China / Fudan University. Shanghai Public Health Clinical Center. Department of Thoracic Surgery. Shanghai, China.); Wen Zilu (Fudan University. Shanghai Emerging and Re-emerging Infectious Disease Institute. Tuberculosis Center. Shanghai, China / Fudan University. Shanghai Public Health Clinical Center. Department of Thoracic Surgery. Shanghai, China.); Elsa du Bruyn (University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Diseases Research in Africa. Cape Town, South Africa.); Catherine Riou (University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Diseases Research in Africa. Cape Town, South Africa.); Keith D. Kauffman (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. T Lymphocyte Biology Section. Bethesda, MD, United States of America.); Tuberculosis Imaging Program (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Division of Intramural Research. Tuberculosis Imaging Program. Bethesda, MD, United States of America.); Ian N. Moore (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Comparative Medicine Branch. Infectious Disease Pathogenesis Section. Bethesda, MD, United States of America.); Franca Del Nonno (Istituto Di Ricovero e Cura a Carattere Scientifico. National Institute for Infectious Diseases "L. Spallanzani". Pathology Unit. Rome, Italy.); Linda Petrone (Istituto Di Ricovero e Cura a Carattere Scientifico. Department of Epidemiology and Preclinical Research National Institute for Infectious Diseases. Translational Research Unit. Rome, Italy.); Delia Goletti (Istituto Di Ricovero e Cura a Carattere Scientifico. Department of Epidemiology and Preclinical Research National Institute for Infectious Diseases. Translational Research Unit. Rome, Italy.); Adrian R. Martineau (University College London. Institute of Immunity and Transplantation. London, United Kingdom.); David M. Lowe (University College London. Institute of Immunity and Transplantation. London, United Kingdom.); Mark R. Cronan (Max Planck Institute for Infection Biology. In Vivo Cell Biology of Infection Unit. Berlin, Germany / Duke University School of Medicine. Department of Molecular Genetics and Microbiology. Durham, NC, United States of America.); Robert J. Wilkinson (University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Diseases Research in Africa. Cape Town, South Africa / Imperial College London. Department of Infectious Diseases. London, United Kingdom.); Clifton E. Barry, III (University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Diseases Research in Africa. Cape Town, South Africa / National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Tuberculosis Research Section. Bethesda, MD, United States of America.); Laura E. Via (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Division of Intramural Research. Tuberculosis Imaging Program. Bethesda, MD, United States of America / National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Tuberculosis Research Section. Bethesda, MD, United States of America.); Daniel L. Barber (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. T Lymphocyte Biology Section. Bethesda, MD, United States of America.); Amy D. Klion (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Human Eosinophil Section. Bethesda, MD, United States of America.); Bruno B. Andrade (The KAB Group / Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.); Yanzheng Song (Fudan University. Shanghai Emerging and Re-emerging Infectious Disease Institute. Tuberculosis Center. Shanghai, China / Fudan University. Shanghai Public Health Clinical Center. Department of Thoracic Surgery. Shanghai, China.); Ka-Wing Wong (Fudan University. Shanghai Public Health Clinical Center. Department of Scientific Research. Shanghai, China / Fudan University. Shanghai Emerging and Re-emerging Infectious Disease Institute. Tuberculosis Center. Shanghai, China.); Katrin D. Mayer-Barber (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Inflammation and Innate Immunity Unit. Bethesda, MD, United States of America).Division of Intramural Research, National Institute of Allergy and Infectious Diseases and the National Natural Science Foundation of China (grant no. 81770010 to K.-W. Wong)National Institutes of Health (grant no. U01AI115940)Wellcome Trust (grant nos. 104803 and 203135)Cancer Research UK, UK Research and Innovation, and Wellcome Trust (FC0010218)National Council for Scientific and Technological Development (senior fellowship)Intramural Research Program of the Oswaldo Cruz Foundation, BrazilHost resistance to Mycobacterium tuberculosis (Mtb) infection requires the activities of multiple leukocyte subsets, yet the roles of the different innate effector cells during tuberculosis are incompletely understood. Here we uncover an unexpected association between eosinophils and Mtb infection. In humans, eosinophils are decreased in the blood but enriched in resected human tuberculosis lung lesions and autopsy granulomas. An influx of eosinophils is also evident in infected zebrafish, mice, and nonhuman primate granulomas, where they are functionally activated and degranulate. Importantly, using complementary genetic models of eosinophil deficiency, we demonstrate that in mice, eosinophils are required for optimal pulmonary bacterial control and host survival after Mtb infection. Collectively, our findings uncover an unexpected recruitment of eosinophils to the infected lung tissue and a protective role for these cells in the control of Mtb infection in mice.2022-02-04