| dc.identifier.uri | http://hdl.handle.net/11401/76537 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.abstract | Immature myeloid cells in the bone marrow are a heterogeneous population of cells that, under normal conditions, provide tissues with protective cell types such as granulocytes, dendritic cells, and macrophages. Under certain pathological conditions, myeloid cell homeostasis is altered and immature forms of these cells appear in significant numbers in tissues. Murine immature myeloid cells that express CD11b and Ly6C or Ly6G have been associated with immunosuppression in cancer and, more recently, infection. Using a murine model of persistent salmonellosis, we found that CD11b+Ly6ChiLy6G- mononuclear and CD11b+ Ly6Cint Ly6G+ polymorphonuclear cells accumulate and persist in tissues of mice infected with the bacterial pathogen Salmonella. The CD11b+Ly6ChiLy6G- cells could differentiate into macrophage-like cells ex vivo and present antigen to T cells in vitro. However, significant proliferation of the T cells was observed only when the ability of the CD11b+Ly6ChiLy6G- cells to produce nitric oxide was blocked. Thus, CD11b+Ly6ChiLy6G- cells recruited in response to persistent salmonellosis exhibit protective and immunosuppressive properties, suggesting that these cells may have a complex role in the host response to infection. Emigration of Ly6Chi monocytes from the bone marrow is dependent on CC-chemokine receptor 2 (CCR2) and largely mediated by CC-chemokine ligand 2 (CCL2, also referred to as MCP1). Here, we found that Ccr2 is required and Ccl2 is important for the recruitment of CD11b+ Ly6Chi Ly6G- monocytic cells into tissues during persistent salmonellosis. In addition, we found that Ccr2- and Ccl2-deficient mice are more susceptible to persistent Salmonella infection than wild-type mice, with Ccr2-deficient mice being more susceptible than Ccl2-deficient mice. Depletion of CCR2+ cells during the first or third week of Salmonella infection increased susceptibility to persistent salmonellosis, indicating that CCR2+ cells, including CD11b+ Ly6Chi Ly6G- monocytic cells, play an essential role in early and late control of Salmonella infection. We propose a model in which CD11b+ Ly6Chi Ly6G- monocytes provide protective functions in the host response to infection, where accumulation and persistence of these cells beyond a certain threshold level may cause collateral effects that prolong or exacerbate disease. | |
| dcterms.available | 2017-09-20T16:50:35Z | |
| dcterms.contributor | Krug, Laurie | en_US |
| dcterms.contributor | van der Velden, Adrianus W. M. | en_US |
| dcterms.contributor | Bliska, James | en_US |
| dcterms.contributor | Konopka, James | en_US |
| dcterms.contributor | Pamer, Eric. | en_US |
| dcterms.creator | Tam, Jason Wayne | |
| dcterms.dateAccepted | 2017-09-20T16:50:35Z | |
| dcterms.dateSubmitted | 2017-09-20T16:50:35Z | |
| dcterms.description | Department of Molecular Genetics and Microbiology. | en_US |
| dcterms.extent | 138 pg. | en_US |
| dcterms.format | Monograph | |
| dcterms.format | Application/PDF | en_US |
| dcterms.identifier | http://hdl.handle.net/11401/76537 | |
| dcterms.issued | 2015-05-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:50:35Z (GMT). No. of bitstreams: 1
Tam_grad.sunysb_0771E_12278.pdf: 25851910 bytes, checksum: 9b2a42ec0217783294ecda03543f24cc (MD5)
Previous issue date: 2015 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Immunology | |
| dcterms.subject | Bacterial Infection, Inflammation, Innate Immunity, Monocytes, Persistent Infection, Salmonella | |
| dcterms.title | On the role of immature myeloid cells in the host response to Salmonella infection | |
| dcterms.type | Dissertation | |
