Lipocalin 2 regulates inflammation during pulmonary mycobacterial infections

• Published in: PloS one Vol. 7; no. 11; p. e50052
• Main Authors: Guglani, Lokesh, Gopal, Radha, Rangel-Moreno, Javier, Junecko, Beth Fallert, Lin, Yinyao, Berger, Thorsten, Mak, Tak W, Alcorn, John F, Randall, Troy D, Reinhart, Todd A, Chan, Yvonne R, Khader, Shabaana A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20-11-2012; Public Library of Science (PLoS)
• Subjects: Accumulation; Acute Disease; Acute-Phase Proteins - deficiency; Acute-Phase Proteins - genetics; Acute-Phase Proteins - immunology; Alveoli; Animal models; Animals; B cells; Bacillus Calmette-Guerin vaccine; Bacteria; Bacterial infections; BCG; Biology; Breast cancer; Cell Movement; Chemokine CXCL9 - antagonists & inhibitors; Chemokine CXCL9 - immunology; Chemokines; Chronic Disease; Cytokines; Drug dosages; Experiments; Gene Expression; Granulocyte colony-stimulating factor; Granuloma; Granuloma, Respiratory Tract - immunology; Granuloma, Respiratory Tract - metabolism; Granuloma, Respiratory Tract - microbiology; Granuloma, Respiratory Tract - veterinary; Health aspects; Health care networks; Immunology; Infection; Infections; Infectious diseases; Inflammation; Inflammation - immunology; Inflammation - metabolism; Inflammation - microbiology; Inflammation - veterinary; Inflammatory response; Iron; Iron - metabolism; Lipocalin; Lipocalin-2; Lipocalins - genetics; Lipocalins - immunology; Lung diseases; Lungs; Lymphocytes; Lymphocytes T; Macrophages; Macrophages, Alveolar - immunology; Macrophages, Alveolar - microbiology; Medical research; Medicine; Mice; Mice, Inbred C57BL; Mice, Knockout; Mycobacterium bovis; Mycobacterium bovis - immunology; Mycobacterium Infections - immunology; Mycobacterium Infections - metabolism; Mycobacterium Infections - microbiology; Mycobacterium Infections - veterinary; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; Neutrophils; Neutrophils - immunology; Neutrophils - microbiology; Oncogene Proteins - deficiency; Oncogene Proteins - genetics; Oncogene Proteins - immunology; Pediatrics; Protein binding; Proteins; Public health; Regulatory mechanisms (biology); Rheumatology; Rodents; Sequestering; Siderophores; Siderophores - metabolism; T cells; T-Lymphocytes - immunology; T-Lymphocytes - microbiology; Tuberculosis; Tuberculosis - immunology; Tuberculosis - metabolism; Tuberculosis - microbiology; Tuberculosis - veterinary; United States > US; Pittsburgh Pennsylvania; Pennsylvania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0050052

Pulmonary tuberculosis (TB), caused by the intracellular bacteria Mycobacterium tuberculosis, is a worldwide disease that continues to kill more than 1.5 million people every year worldwide. The accumulation of lymphocytes mediates the formation of the tubercle granuloma in the lung and is crucial for host protection against M.tuberculosis infection. However, paradoxically the tubercle granuloma is also the basis for the immunopathology associated with the disease and very little is known about the regulatory mechanisms that constrain the inflammation associated with the granulomas. Lipocalin 2 (Lcn2) is a member of the lipocalin family of proteins and binds to bacterial siderophores thereby sequestering iron required for bacterial growth. Thus far, it is not known whether Lcn2 plays a role in the inflammatory response to mycobacterial pulmonary infections. In the present study, using models of acute and chronic mycobacterial pulmonary infections, we reveal a novel role for Lcn2 in constraining T cell lymphocytic accumulation and inflammation by inhibiting inflammatory chemokines, such as CXCL9. In contrast, Lcn2 promotes neutrophil recruitment during mycobacterial pulmonary infection, by inducing G-CSF and KC in alveolar macrophages. Importantly, despite a common role for Lcn2 in regulating chemokines during mycobacterial pulmonary infections, Lcn2 deficient mice are more susceptible to acute M.bovis BCG, but not low dose M.tuberculosis pulmonary infection.