This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This project will test the hypothesis that deposition of Pneumocystis carinii in the respiratory tract stimulates release of IL-23 followed by downstream release of IFN and granulocyte/macrophage colony stimulating factor (GM-CSF) leading to clearance of infection. We will also test the concept that gene transfer of IL-23 can provide a novel form of immune enhancement during states of immunodeficiency. To test this hypostesis, the following specific aims will be performed:
In Specific Aim 1, we will localize cellular sources of IL-23 in lung tissue at serial intervals after inoculation of P. carinii.
In Specific Aim 2, we will demonstrate that neutralization of IL-23 using a soluble inhibitory RNA approach will compromise host defense against infection.
In Specific Aim 3, we will identify downstream inflammatory cytokines, specifically IFN and GM-CSF, in lung tissue in response to IL-23.
In Specific Aim 4, we will demonstrate that local delivery of IL-23 by gene transfer will enhance clearance of infection in normal mice and, in particular, ameliorate infection in mice depleted of CD4+ T-lymphocytes.
|Rodriguez, Paulo C; Ochoa, Augusto C; Al-Khami, Amir A (2017) Arginine Metabolism in Myeloid Cells Shapes Innate and Adaptive Immunity. Front Immunol 8:93|
|Sanchez, Maria Dulfary; Ochoa, Augusto C; Foster, Timothy P (2016) Development and evaluation of a host-targeted antiviral that abrogates herpes simplex virus replication through modulation of arginine-associated metabolic pathways. Antiviral Res 132:13-25|
|Dai, Lu; Bai, Lihua; Lin, Zhen et al. (2016) Transcriptomic analysis of KSHV-infected primary oral fibroblasts: The role of interferon-induced genes in the latency of oncogenic virus. Oncotarget 7:47052-47060|
|Schieffelin, John; Moses, Lina M; Shaffer, Jeffrey et al. (2016) Clinical validation trial of a diagnostic for Ebola Zaire antigen detection: Design rationale and challenges to implementation. Clin Trials 13:66-72|
|Fletcher, Matthew; Ramirez, Maria E; Sierra, Rosa A et al. (2015) l-Arginine depletion blunts antitumor T-cell responses by inducing myeloid-derived suppressor cells. Cancer Res 75:275-83|
|Dai, Lu; Trillo-Tinoco, Jimena; Bai, Aiping et al. (2015) Ceramides promote apoptosis for virus-infected lymphoma cells through induction of ceramide synthases and viral lytic gene expression. Oncotarget 6:24246-60|
|Geng, Degui; Kaczanowska, Sabina; Tsai, Alexander et al. (2015) TLR5 Ligand-Secreting T Cells Reshape the Tumor Microenvironment and Enhance Antitumor Activity. Cancer Res 75:1959-1971|
|Dai, Lu; Chen, Yihan; Bonstaff, Karlie et al. (2015) Induction of hyaluronan production by oncogenic KSHV and the contribution to viral pathogenesis in AIDS patients. Cancer Lett 362:158-66|
|Dai, Lu; Trillo-Tinoco, Jimena; Cao, Yueyu et al. (2015) Targeting HGF/c-MET induces cell cycle arrest, DNA damage, and apoptosis for primary effusion lymphoma. Blood 126:2821-31|
|Dai, Lu; Cao, Yueyu; Chen, Yihan et al. (2015) Genomic analysis of xCT-mediated regulatory network: Identification of novel targets against AIDS-associated lymphoma. Oncotarget 6:12710-22|
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