title: LAG3 expression in active Mycobacterium tuberculosis infections.
abstract: Mycobacterium tuberculosis (MTB) is a highly successful pathogen because of its ability to persist in human lungs for long periods of time. MTB modulates several aspects of the host immune response. Lymphocyte-activation gene 3 (LAG3) is a protein with a high affinity for the CD4 receptor and is expressed mainly by regulatory T cells with immunomodulatory functions. To understand the function of LAG3 during MTB infection, a nonhuman primate model of tuberculosis, which recapitulates key aspects of natural human infection in rhesus macaques (Macaca mulatta), was used. We show that the expression of LAG3 is highly induced in the lungs and particularly in the granulomatous lesions of macaques experimentally infected with MTB. Furthermore, we show that LAG3 expression is not induced in the lungs and lung granulomas of animals exhibiting latent tuberculosis infection. However, simian immunodeficiency virus-induced reactivation of latent tuberculosis infection results in an increased expression of LAG3 in the lungs. This response is not observed in nonhuman primates infected with non-MTB bacterial pathogens, nor with simian immunodeficiency virus alone. Our data show that LAG3 was expressed primarily on CD4(+) T cells, presumably by regulatory T cells but also by natural killer cells. The expression of LAG3 coincides with high bacterial burdens and changes in the host type 1 helper T-cell response.
authors.affiliation: Division of Bacteriology, Tulane National Primate Research Center, Covington, Louisiana; Biomedical Sciences Graduate Student Program, New Orleans, Louisiana; National Institute of Respiratory Diseases, Mexico City, Mexico.
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Phillips
authors.affiliation: Division of Microbiology, Tulane National Primate Research Center, Covington, Louisiana.
authors.forename: Smriti
authors.initials: S
authors.lastname: Mehra
authors.affiliation: Division of Bacteriology, Tulane National Primate Research Center, Covington, Louisiana; Training in Lung Molecular and Cell Pathobiology Program, New Orleans, Louisiana.
authors.forename: Muhammad H
authors.initials: MH
authors.lastname: Ahsan
authors.affiliation: National Institute of Respiratory Diseases, Mexico City, Mexico.
authors.forename: Moises
authors.initials: M
authors.lastname: Selman
authors.affiliation: Department of Molecular Microbiology and Immunology, Washington University of St. Louis, St. Louis, Missouri.
authors.forename: Shabaana A
authors.initials: SA
authors.lastname: Khader
authors.affiliation: Division of Bacteriology, Tulane National Primate Research Center, Covington, Louisiana; Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana. Electronic address: dkaushal@tulane.edu.
authors.forename: Deepak
authors.initials: D
authors.lastname: Kaushal
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D055985:Latent Tuberculosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008253:Macaca mulatta; D009169:Mycobacterium tuberculosis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism / Q000473:pathology; D014376:Tuberculosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D000093322:Lymphocyte Activation Gene 3 Protein