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Am J Respir Cell Mol Biol. 2017 Nov 15. doi: 10.1165/rcmb.2017-0021OC. [Epub ahead of print]
Neutrophil Mediated Suppression of Influenza-induced Pathology Requires CD11b/CD18 (MAC-1).
Tak T1, Rygiel TP2,3, Karnam G4, Bastian OW5, Boon L6, Viveen M7, Coenjaerts FE8, Meyaard L9, Koenderman L10, Pillay J11.
Author information
Abstract
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 Mac-1 (CD11b/CD18). Therefore, we tested the hypothesis that immune suppression by neutrophils can reduce T-cell mediate 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 to 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 to 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.
KEYWORDS:
cd11b; influenza; neutrophils
PMID: 29141155 DOI: 10.1165/rcmb.2017-0021OC
Neutrophil Mediated Suppression of Influenza-induced Pathology Requires CD11b/CD18 (MAC-1).
Tak T1, Rygiel TP2,3, Karnam G4, Bastian OW5, Boon L6, Viveen M7, Coenjaerts FE8, Meyaard L9, Koenderman L10, Pillay J11.
Author information
Abstract
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 Mac-1 (CD11b/CD18). Therefore, we tested the hypothesis that immune suppression by neutrophils can reduce T-cell mediate 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 to 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 to 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.
KEYWORDS:
cd11b; influenza; neutrophils
PMID: 29141155 DOI: 10.1165/rcmb.2017-0021OC