Newborn mice are unable to clear Pneumocystis (PC) infection with the same efficiency as adults due, in part, to their inability to develop a robust immune response to infection until three weeks of age. It is known that infants tend develop a Th2 skewed response to antigen so we sought to determine whether a biased cytokine response altered the clearance of PC infection in neonatal mice. P. murina infection in neonatal mice resulted in increased IL-4 expression by CD4 T cells and myeloid cells, augmented IL-13 secretion within the airways and increased arginase activity in the airways, indicative of Th2-type responses. P. murina-infected IL-4Rα−/− neonates had a shift towards Th1 cytokine production and increased numbers of CD4 and CD8 T cells within the lung as well as elevated levels of P. murina-specific IgG. IFNγ−/− and IL-23 p19−/− mice had altered CD4-T cell-dependent cytokine and cell responses. Though we could alter the T helper cell environment in neonatal knockout mice, there was no loss in the ability of these pups to clear infection. It is possible that the Th2 phenotype normally seen in neonatal mice protects the developing lung from pro-inflammatory immune responses without compromising host defense against P. murina.
Digital Object Identifier (DOI)
This work was funded by Public Health Service grant HL62053 from the National Heart, Lung and Blood Institute and AI46016 from the National Institute of Allergy and Infectious Diseases to B.A.G.
The data presented in this study are shown in the manuscript published here. Raw data are available upon request from the corresponding author.
Kurkjian, Cathryn J.; Hollifield, Melissa L.; Feola, David J.; and Garvy, Beth A., "Bias of the Immune Response to Pneumocystis murina Does Not Alter the Ability of Neonatal Mice to Clear the Infection" (2021). Microbiology, Immunology, and Molecular Genetics Faculty Publications. 151.