title: Eosinophils Contribute to Early Clearance of Pneumocystis murina Infection.
abstract: Pneumocystis pneumonia remains a common opportunistic infection in the diverse immunosuppressed population. One clear risk factor for susceptibility to Pneumocystis is a declining CD4(+) T cell count in the setting of HIV/AIDS or primary immunodeficiency. Non-HIV-infected individuals taking immunosuppressive drug regimens targeting T cell activation are also susceptible. Given the crucial role of CD4(+) T cells in host defense against Pneumocystis, we used RNA sequencing of whole lung early in infection in wild-type and CD4-depleted animals as an unbiased approach to examine mechanisms of fungal clearance. In wild-type mice, a strong eosinophil signature was observed at day 14 post Pneumocystis challenge, and eosinophils were increased in the bronchoalveolar lavage fluid of wild-type mice. Furthermore, eosinophilopoiesis-deficient Gata1(tm6Sho)/J mice were more susceptible to Pneumocystis infection when compared with BALB/c controls, and bone marrow-derived eosinophils had in vitro Pneumocystis killing activity. To drive eosinophilia in vivo, Rag1(-/-) mice were treated with a plasmid expressing IL-5 (pIL5) or an empty plasmid control via hydrodynamic injection. The pIL5-treated mice had increased serum IL-5 and eosinophilia in the lung, as well as reduced Pneumocystis burden, compared with mice treated with control plasmid. In addition, pIL5 treatment could induce eosinophilia and reduce Pneumocystis burden in CD4-depleted C57BL/6 and BALB/c mice, but not eosinophilopoiesis-deficient Gata1(tm6Sho)/J mice. Taken together, these results demonstrate that an early role of CD4(+) T cells is to recruit eosinophils to the lung and that eosinophils are a novel candidate for future therapeutic development in the treatment of Pneumocystis pneumonia in the immunosuppressed population.
authors.affiliation: Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224; Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA 15224;
authors.forename: Taylor
authors.initials: T
authors.lastname: Eddens
authors.affiliation: Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224; Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA 15224;
authors.forename: Waleed
authors.initials: W
authors.lastname: Elsegeiny
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294; and.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Nelson
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA 15224;
authors.forename: William
authors.initials: W
authors.lastname: Horne
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA 15224; Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Campfield
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294; and jay.kolls@chp.edu chadsteele@uab.edu.
authors.forename: Chad
authors.initials: C
authors.lastname: Steele
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA 15224; jay.kolls@chp.edu chadsteele@uab.edu.
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D004804:Eosinophils / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005260:Female; D050982:GATA1 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D015316:Genetic Therapy; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology*; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010957:Plasmids / Q000008:administration & dosage / Q000276:immunology; D011010:Pneumocystis / Q000276:immunology*; D011020:Pneumonia, Pneumocystis / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D013997:Time Factors
chemical_list: D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D018398:Homeodomain Proteins; D015848:Interleukin-5; C064658:RAG-1 protein