American journal of respiratory cell and molecular biology 2017 11 15() 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 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.