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Mucosal and Systemic Immune Phenotype is Altered During HIV-1 Infection and is Partially Restored and Further Disrupted in the Absence of Detectable Viral Replication

McCausland, Marie Rose
http://rave.ohiolink.edu/etdc/view?acc_num=case1473679665919823

Abstract Details

2017, Doctor of Philosophy, Case Western Reserve University, Molecular Biology and Microbiology.
Human Immunodeficiency Virus (HIV) infection, while now treatable with antiretroviral therapy (ART), remains a problem for millions of patients worldwide. Patients on ART continue to have an increased risk of Acquired Immunodeficiency Syndrome (AIDS)-related and non-AIDS-related diseases such as cardiovascular disease, cancer, and neurocognitive defects. One potential reason for the increased morbidity and mortality seen in HIV (+) patients is the intestinal barrier defect known to be present in these patients. Decreased barrier function allows for microbial translocation, localized inflammation, partially due to Toll-Like receptor (TLR) ligation, and eventually systemic immune activation. We analyzed the phenotype of monocytes, known players in cardiovascular disease which travel to sites of inflammation, by flow cytometry, as well as TLR phenotype in the colon by immunofluorescence. Our results showed an increase in monocyte activation (HLA-DR, CD86) and decreased chemokine receptor expression (CCR2, CX3CR1) in viremic HIV (+) patients when compared to uninfected controls, which was only partially normalized with ART. Additionally, CD40 is further disrupted on monocytes with ART. Similarly, we find increased TLR3, TLR4, and TLR9 expression in the colons of Viremic HIV (+) patients, whose abundance and location do not fully normalize (TLR4, TLR9), or was further disrupted by ART (TLR3). Together our data suggest that ART, which is successful at controlling viral replication in tissue and HIV RNA levels found in the blood, does not allow for normalization of the immune activation seen in the HIV (+) patients, and in fact could be contributing to the continued pathology.
Alan Levine (Advisor)
John Tilton (Committee Chair)
David McDonald (Committee Member)
Calvin Cotton (Committee Member)
146 p.
Immunology; Pathology; Virology
HIV; Antiretroviral therapy; TLRs; Toll-Like Receptors; Monocyte;

Recommended Citations

Citations

  • McCausland, M. R. (2017). Mucosal and Systemic Immune Phenotype is Altered During HIV-1 Infection and is Partially Restored and Further Disrupted in the Absence of Detectable Viral Replication [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1473679665919823

    APA Style (7th edition)

  • McCausland, Marie. Mucosal and Systemic Immune Phenotype is Altered During HIV-1 Infection and is Partially Restored and Further Disrupted in the Absence of Detectable Viral Replication. 2017. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1473679665919823.

    MLA Style (8th edition)

  • McCausland, Marie. "Mucosal and Systemic Immune Phenotype is Altered During HIV-1 Infection and is Partially Restored and Further Disrupted in the Absence of Detectable Viral Replication." Doctoral dissertation, Case Western Reserve University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1473679665919823

    Chicago Manual of Style (17th edition)

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© 2017, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.