Delayed inflammatory response to Pneumocystis carinii infection in neonatal mice is due to an inadequate lung environment.
Challenge of neonatal mice with an intranasal inoculation of Pneumocystis carinii results in a subclinical infection that takes 6 wk to resolve, whereas adult mice resolve a comparable challenge within 3 wk. This delayed clearance is due to a delayed inflammatory response in neonatal mice; however, the reason for this delay has been unknown. To determine whether the neonatal lung environment is sufficient to attract immunocompetent lymphocytes into the lungs, an adoptive transfer strategy was employed in which splenocytes from adult BALB/c mice were transferred into P. carinii-infected neonatal or adult SCID mice. All adults, but no pups, resolved their infections by day 37 postreconstitution. Despite reconstitution with adult splenocytes, pups had a negligible lung inflammatory response until day 24, whereas adult mice had activated CD4(+) and CD8(+) cells in the lung by day 13. The delay in neonates corresponded to delayed kinetics of expression of lung cytokines TNF-alpha and IFN-gamma mRNA and chemokines lymphotactin, RANTES, and macrophage inflammatory protein-1ss mRNA. Phagocytic cells from neonatal mice were significantly less efficient than adult cells at migrating to the draining lymph nodes after phagocytosing fluorescent beads. There were fewer dendritic cells and Ia(+) myeloid cells in the lungs of P. carinii-infected neonatal mice compared with adults. These data indicate that the lung environment of neonatal mice is insufficient for migration of T cells, due at least in part to inefficient phagocytosis and migration of APCs to the lymph nodes as well as delayed chemokine and TNF-alpha mRNA expression.
Garvy
B A
BA
Department of Internal Medicine, Division of Infectious Diseases, University of Kentucky and Veterans Affairs Medical Center, Lexington, KY 40506, USA. bgarv0@pop.uky.edu
Qureshi
M H
MH
D019264:Adoptive Transfer; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology* / Q000382:microbiology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D011010:Pneumocystis / Q000276:immunology; D011020:Pneumonia, Pneumocystis / Q000209:etiology / Q000276:immunology* / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000637:transplantation
D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger