Modulation of proinflammatory responses to Pneumocystis carinii f. sp. muris in neonatal mice by granulocyte-macrophage colony-stimulating factor and IL-4: role of APCs.
Clearance of Pneumocystis carinii f. sp. muris (PC) organisms from the lungs of neonatal mice is delayed due to failure of initiation of inflammation over the first 3 wk after infection. The ability of neonatal lung CD11c(+) dendritic cells (DCs) to induce Ag-specific T cell proliferative responses was significantly reduced compared with adult lung DCs. However, neonatal bone marrow-derived DCs were as competent at presenting PC Ag as were adult bone marrow-derived DCs. Because GM-CSF mRNA expression and activity were significantly reduced in neonatal lungs compared with adults, we treated neonates with exogenous GM-CSF and IL-4 and found enhanced clearance of PC compared with untreated neonates. This was associated with increased lung TNF-alpha, IL-12p35, and IL-18 mRNA expression, indicating enhanced innate immune responses. Cytokine-treated mice had marked expansion of CD11c(+) DCs with up-regulated MHC-II in the lungs. Moreover, increased numbers of activated CD4(+)CD44(high)CD62L(low) cells in the lungs and draining lymph nodes suggested improved Ag presentation by the APCs. Together these data indicate that neonatal lungs lack maturation factors for efficient cellular functioning, including APC maturation.
Qureshi
Mahboob H
MH
Department of Microbiology, University of Kentucky, Lexington, KY 40536, USA. mqureshi@touro.edu
Empey
Kerry M
KM
Garvy
Beth A
BA
D000818:Animals; D000831:Animals, Newborn; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology* / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D016720:Pneumocystis Infections / Q000276:immunology*; D045363:Pneumocystis carinii / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis
D012333:RNA, Messenger; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor