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The Role of CD169 and B-1 Cells in M...

Pi, Ruoxi .

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The Role of CD169 and B-1 Cells in Murine Retrovirus Infection.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The Role of CD169 and B-1 Cells in Murine Retrovirus Infection./
作者:	Pi, Ruoxi .
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:	213 p.
附註:	Source: Dissertations Abstracts International, Volume: 81-10, Section: B.
Contained By:	Dissertations Abstracts International81-10B.
標題:	Microbiology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=27540687
ISBN:	9798607315689

The Role of CD169 and B-1 Cells in Murine Retrovirus Infection.
Pi, Ruoxi .

The Role of CD169 and B-1 Cells in Murine Retrovirus Infection. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 213 p.

Source: Dissertations Abstracts International, Volume: 81-10, Section: B.

Thesis (Ph.D.)--Yale University, 2019.

This item must not be sold to any third party vendors.

Retroviruses are infectious agents that cause cancer and immunodeficiency in many animal species. The early events during retroviral infection are critical to the establishment of viral infection in primary draining lymphoid tissue as well as the subsequent systemic spread of the viruses in the host. In our previous study, with murine leukemia virus (MLV), we illustrated the early events of retroviral infection in its natural host. After the entry into the host, lymph- and blood-borne MLV gets captured rapidly at primary draining lymph node by subcapsular sinus (SCS) macrophages and at spleen by metallophilic macrophages, respectively. The interaction of MLV particles with both populations of macrophages is mediated by the gangliosides incorporated into the virions and CD169/Siglec-1 expressed by the macrophages. MLV-laden CD169+ macrophages subsequently trans-infect B-1 cells in the lymph node, which facilitates the establishment of MLV infection. However, the role of CD169+ macrophages in systemic spread as well as in pathogenesis of murine retroviruses is not known. In addition, why MLV initially infects B-1 cells is unknown.In this thesis, studying a pathogenic splenomegaly-inducing murine retrovirus, the Friend virus complex (FVC), we have demonstrated that CD169+ macrophages play a protective role against retroviral pathogenesis. CD169+ macrophages in primary draining lymph node efficiently absorbed lymph-borne FVC and reduced the systemic spread of cell-free virus into blood and spleen. At the spleen, CD169+ macrophages captured blood-borne FVC and limited its spread to erythroblasts in red pulp, where FVC manifests its pathogenesis. Retrovirus-laden CD169+ macrophages interacted with conventional dendritic cell 1 (cDC1s) and promoted the cross-priming of cytotoxic CD8+ T cells, which is critical for the clearance of FVC-infected cells. Functional blockade of CD169 in primary draining lymph node accelerated the death in a susceptible mouse strain after FVC challenge. Collectively, we have illustrated a protective role of CD169 against pathogenic FVC infection both in limiting viral spread into erythroblast niche and in efficiently mounting cell-mediated immune response. The second part of my thesis is devoted to understanding why B-1 cells in draining lymph nodes are highly susceptible to FrMLV infection following s.c. infections. We used a mouse strain that is deficient in B-1 cell population (bumble, IkBNS-/-) to study the function of B-1 cells. FrMLV infection in bumble mice was significantly reduced compared to wild-type mice. An adoptive transfer of wild-type B-1 cells but not Tlr7-/- or Ifnar1-/- B-1 cells into bumble mice rescued FrMLV infection, suggesting that TLR7-mediated sensing as well as intrinsic type I IFN signaling are critical to the susceptibility of B-1 cells to FrMLV infection. The reduced FrMLV infection in bumble mice was mainly due to a compromised spread of FrMLV into B-2 cell population. Infected B-1 cell migrated to medullary cord where they were found in proximity to infected B-2 cells. These data revealed that retroviruses can exploit the innate-immune sensing in target cells to facilitate its infection. It also suggests that retroviruses can utilize an intrinsically susceptible cell type for the propagation of infection in lymphoid tissue. Together my work illustrates how CD169+ macrophages cooperate with either cDC1s or B-1 cells to promote protective CD8+ T cell responses or viral dissemination.

ISBN: 9798607315689Subjects--Topical Terms:

536250
Microbiology.
Subjects--Index Terms:

B-1 cells

The Role of CD169 and B-1 Cells in Murine Retrovirus Infection.
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