The migration of T cells in response to influenza virus is altered in neonatal mice.
Influenza virus is a significant cause of mortality and morbidity in children; however, little is known about the T cell response in infant lungs. Neonatal mice are highly vulnerable to influenza and only control very low doses of virus. We compared the T cell response to influenza virus infection between mice infected as adults or at 2 d old and observed defective migration into the lungs of the neonatal mice. In the adult mice, the numbers of T cells in the lung interstitia peaked at 10 d postinfection, whereas neonatal T cell infiltration, activation, and expression of TNF-alpha was delayed until 2 wk postinfection. Although T cell numbers ultimately reached adult levels in the interstitia, they were not detected in the alveoli of neonatal lungs. Instead, the alveoli contained eosinophils and neutrophils. This altered infiltrate was consistent with reduced or delayed expression of type 1 cytokines in the neonatal lung and differential chemokine expression. In influenza-infected neonates, CXCL2, CCL5, and CCL3 were expressed at adult levels, whereas the chemokines CXCL1, CXCL9, and CCL2 remained at baseline levels, and CCL11 was highly elevated. Intranasal administration of CCL2, IFN-gamma, or CXCL9 was unable to draw the neonatal T cells into the airways. Together, these data suggest that the T cell response to influenza virus is qualitatively different in neonatal mice and may contribute to an increased morbidity.
Lines
J Louise
JL
Department of Microbiology, Immunology, and Molecular Genetics, College of Medicine, University of Kentucky, Lexington, KY 40506, USA.
Hoskins
Samantha
S
Hollifield
Melissa
M
Cauley
Linda S
LS
Garvy
Beth A
BA
D000818:Animals; D000831:Animals, Newborn; D049109:Cell Proliferation; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology / Q000473:pathology / Q000821:virology; D005260:Female; D020022:Genetic Predisposition to Disease; D009980:Influenza A virus / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology / Q000473:pathology / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology; D011650:Pulmonary Alveoli / Q000276:immunology / Q000473:pathology / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology / Q000821:virology*