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Defining Dendritic Cells and Macrophages in Lymph Nodes and Gut Mucosa During Simian Immunodeficiency Virus Infection

Swan, Zachary Duane Jameson (2012) Defining Dendritic Cells and Macrophages in Lymph Nodes and Gut Mucosa During Simian Immunodeficiency Virus Infection. Master's Thesis, University of Pittsburgh. (Unpublished)

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The gut mucosa is an important site of virus replication and immune activation in individuals infected with human immunodeficiency virus (HIV), but the impact of infection on innate immune cells within the gut and gut-draining mesenteric lymph nodes (LN) is ill-defined. To address this gap in knowledge, we studied rhesus macaques infected with pathogenic simian immunodeficiency virus (SIV), which is a highly relevant model of HIV infection and AIDS. We analyzed macrophage, myeloid dendritic cell (mDC), and plasmacytoid dendritic cell (pDC) subsets in LN and terminal ileum samples taken from naive rhesus macaques and macaques infected with SIVmac251 with and without antiretroviral therapy (ART) to reduce virus load. CD163-CD68+ macrophages did not fluctuate with disease, while putative anti-inflammatory CD163+CD68+ macrophages were significantly increased in mesenteric and peripheral LN, which may be suggestive of the host’s attempt to repress inflammation. CD11c+ mDC and CD123+ pDC in peripheral LN exhibited a modest decrease during acute SIV infection and AIDS. Lastly, we determined the percentage of CD103+ DC, which have been shown to induce regulatory T cell (Treg) differentiation in mesenteric LN and imprint Treg with gut-homing markers. CD103 was expressed on 31% of mDC in mesenteric LN of healthy macaques and a similar proportion of mDC in SIV-infected animals receiving therapy, whereas CD103+ mDC were depleted in untreated SIV infection, suggesting a role for CD103+ mDC loss in altering Treg homeostasis. Our results highlight the complexity of the innate immune response to SIV in mucosal tissues and point to contributions of macrophages and DC in virus control and AIDS pathogenesis. These findings could lead to discoveries of novel innate immune therapeutic targets and therefore have significant public health value.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Swan, Zachary Duane Jamesonzds8@pitt.eduZDS8
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorBarratt-Boyes, Simon M. smbb@pitt.eduSMBB
Committee MemberReinhart, Todd A. reinhar@pitt.eduREINHAR
Committee MemberMurphey-Corb, Michael A.mcorb@pitt.eduMCORB
Date: 21 September 2012
Date Type: Publication
Defense Date: 19 April 2012
Approval Date: 21 September 2012
Submission Date: 4 April 2012
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 84
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: HIV; SIV; dendritic cells; macrophages; lymph nodes; gut
Date Deposited: 21 Sep 2012 15:14
Last Modified: 15 Nov 2016 13:57


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