Influenza A virus infection inhibits the efficient recruitment of Th2 cells into the airways and the development of airway eosinophilia.
Most infections with respiratory viruses induce Th1 responses characterized by the generation of Th1 and CD8(+) T cells secreting IFN-gamma, which in turn have been shown to inhibit the development of Th2 cells. Therefore, it could be expected that respiratory viral infections mediate protection against asthma. However, the opposite seems to be true, because viral infections are often associated with the exacerbation of asthma. For this reason, we investigated what effect an influenza A (flu) virus infection has on the development of asthma. We found that flu infection 1, 3, 6, or 9 wk before allergen airway challenge resulted in a strong suppression of allergen-induced airway eosinophilia. This effect was associated with strongly reduced numbers of Th2 cells in the airways and was not observed in IFN-gamma- or IL-12 p35-deficient mice. Mice infected with flu virus and immunized with OVA showed decreased IL-5 and increased IFN-gamma, eotaxin/CC chemokine ligand (CCL)11, RANTES/CCL5, and monocyte chemoattractant protein-1/CCL2 levels in the bronchoalveolar lavage fluid, and increased airway hyperreactivity compared with OVA-immunized mice. These results suggest that the flu virus infection reduced airway eosinophilia by inducing Th1 responses, which lead to the inefficient recruitment of Th2 cells into the airways. However, OVA-specific IgE and IgG1 serum levels, blood eosinophilia, and goblet cell metaplasia in the lung were not reduced by the flu infection. Flu virus infection also directly induced AHR and goblet cell metaplasia. Taken together, our results show that flu virus infections can induce, exacerbate, and suppress features of asthmatic disease in mice.
Wohlleben
Gisela
G
Center for Infectious Diseases and. Department of Pathology, University of Würzburg, Würzburg, Germany.
Müller
Justus
J
Tatsch
Ursula
U
Hambrecht
Christine
C
Herz
Udo
U
Renz
Harald
H
Schmitt
Edgar
E
Moll
Heidrun
H
Erb
Klaus J
KJ
D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D054413:Chemokine CCL11; D018932:Chemokine CCL2 / Q000096:biosynthesis; D018946:Chemokine CCL5 / Q000096:biosynthesis; D019742:Chemokines, CC / Q000096:biosynthesis; D015536:Down-Regulation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D020397:Goblet Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D009980:Influenza A virus / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D015848:Interleukin-5 / Q000037:antagonists & inhibitors; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000276:immunology / Q000821:virology; D008679:Metaplasia; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009559:Nippostrongylus / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D017206:Strongylida Infections / Q000276:immunology / Q000821:virology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D015854:Up-Regulation / Q000276:immunology
D000485:Allergens; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D019742:Chemokines, CC; D018984:Epitopes, T-Lymphocyte; D015848:Interleukin-5; C111390:OVA 323-339; D010446:Peptide Fragments; D007371:Interferon-gamma; D010047:Ovalbumin