Neutrophil-mediated Suppression of Influenza-induced Pathology Requires CD11b/CD18 (MAC-1)

• Published in: American journal of respiratory cell and molecular biology Vol. 58; no. 4; pp. 492 - 499
• Main Authors: Tak, Tamar, Rygiel, Tomasz P, Karnam, Guruswamy, Bastian, Okan W, Boon, Louis, Viveen, Marco, Coenjaerts, Frank E, Meyaard, Linde, Koenderman, Leo, Pillay, Janesh
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01-04-2018
• Subjects: Adoptive Transfer; Animal models; Animals; Bone marrow; CD11b antigen; CD11b Antigen - genetics; CD11b Antigen - immunology; CD11b Antigen - metabolism; CD18 antigen; CD18 Antigens - immunology; CD18 Antigens - metabolism; Chemotaxis, Leukocyte; Disease Models, Animal; Female; Host-Pathogen Interactions; Hypotheses; Immunoglobulins; Immunohistochemistry; Infections; Influenza; Influenza A virus - immunology; Influenza A virus - pathogenicity; Laboratories; Leukocytes (neutrophilic); Lung - immunology; Lung - metabolism; Lung - pathology; Lung - virology; Lungs; Lymphocytes; Lymphocytes T; Mac1 protein; Macrophage-1 Antigen - genetics; Macrophage-1 Antigen - immunology; Macrophage-1 Antigen - metabolism; Macrophages; Mice, Inbred C57BL; Mice, Transgenic; Neutrophils; Neutrophils - immunology; Neutrophils - metabolism; Neutrophils - transplantation; Neutrophils - virology; Orthomyxoviridae Infections - genetics; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - metabolism; Orthomyxoviridae Infections - virology; Pathogens; Pathology; Rodents; Signal Transduction; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - virology; Time Factors; Viral Load; Viruses; Weight Loss; influenza; neutrophils; CD11b
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/rcmb.2017-0021OC

Severe influenza virus infection can lead to life-threatening pathology through immune-mediated tissue damage. In various experimental models, this damage is dependent on T cells. There is conflicting evidence regarding the role of neutrophils in influenza-mediated pathology. Neutrophils are often regarded as cells causing tissue damage, but, in recent years, it has become clear that a subset of human neutrophils is capable of suppressing T cells, which is dependent on macrophage-1 antigen (CD11b/CD18). Therefore, we tested the hypothesis that immune suppression by neutrophils can reduce T cell-mediated pathology after influenza infection. Wild-type (WT) and CD11b
mice were infected with A/HK/2/68 (H3N2) influenza virus. Disease severity was monitored by weight loss, leukocyte infiltration, and immunohistochemistry. We demonstrated that CD11b
mice suffered increased weight loss compared with WT animals upon infection with influenza virus. This was accompanied by increased pulmonary leukocyte infiltration and lung damage. The exaggerated pathology in CD11b
mice was dependent on T cells, as it was reduced by T cell depletion. In addition, pathology in CD11b
mice was accompanied by higher numbers of T cells in the lungs early during infection compared with WT mice. Importantly, these differences in pathology were not associated with an increased viral load, suggesting that pathology was immune-mediated rather than caused by virus-induced damage. In contrast to adoptive transfer of CD11b
neutrophils, a single adoptive transfer of WT neutrophils partly restored protection against influenza-induced pathology, demonstrating the importance of neutrophil CD11b/CD18. Our data show that neutrophil CD11b/CD18 limits pathology in influenza-induced, T cell-mediated disease.