Murine cytomegalovirus infection alters Th1/Th2 cytokine expression, decreases airway eosinophilia, and enhances mucus production in allergic airway disease.
Concomitant infection of murine CMV (MCMV), an opportunistic respiratory pathogen, altered Th1/Th2 cytokine expression, decreased bronchoalveolar lavage (BAL) fluid eosinophilia, and increased mucus production in a murine model of OVA-induced allergic airway disease. Although no change in the total number of leukocytes infiltrating the lung was observed between challenged and MCMV/challenged mice, the cellular profile differed dramatically. After 10 days of OVA-aerosol challenge, eosinophils comprised 64% of the total leukocyte population in BAL fluid from challenged mice compared with 11% in MCMV/challenged mice. Lymphocytes increased from 11% in challenged mice to 30% in MCMV/challenged mice, and this increase corresponded with an increase in the ratio of CD8(+) to CD4(+)TCRalphabeta lymphocytes. The decline in BAL fluid eosinophilia was associated with a change in local Th1/Th2 cytokine profiles. Enhanced levels of IL-4, IL-5, IL-10, and IL-13 were detected in lung tissue from challenged mice by RNase protection assays. In contrast, MCMV/challenged mice transiently expressed elevated levels of IFN-gamma and IL-10 mRNAs, as well as decreased levels of IL-4, IL-5, and IL-13 mRNAs. Elevated levels of IFN-gamma and reduced levels of IL-5 were also demonstrated in BAL fluid from MCMV/challenged mice. Histological evaluation of lung sections revealed extensive mucus plugging and epithelial cell hypertrophy/hyperplasia only in MCMV/challenged mice. Interestingly, the development of airway hyperresponsiveness was observed in challenged mice, not MCMV/challenged mice. Thus, MCMV infection can modulate allergic airway inflammation, and these findings suggest that enhanced mucus production may occur independently of BAL fluid eosinophilia.
Wu
C A
CA
Department of Medicine, University of Connecticut School of Medicine, Farmington, CT 06030, USA. cawu@nso1.uchc.edu
Puddington
L
L
Whiteley
H E
HE
Yiamouyiannis
C A
CA
Schramm
C M
CM
Mohammadu
F
F
Thrall
R S
RS
D000818:Animals; D001249:Asthma / Q000150:complications* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000473:pathology; D005260:Female; D006801:Humans; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009093:Mucus / Q000502:physiology; D010047:Ovalbumin / Q000097:blood / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D012333:RNA, Messenger; D010047:Ovalbumin