Venereal syphilis is a chronic inflammatory disorder driven by the persistence of its etiologic agent Treponema pallidum. Though the immune/inflammatory response at sites of local treponemal infection may ultimately underlie the development of both protective immunity and clinical manifestations, these local cellular processes have yet to be characterized in humans using the tools of contemporary cellular and molecular immunology. The components of T. pallidum that induce these potentially deleterious inflammatory processes also remain poorly characterized. Our understanding of cellular immunity in syphilis is further compromised by our currently limited knowledge concerning the interactions between syphilis and HIV infection. Accordingly, the proposed research has three Specific Aims.
In Specific Aim 1, we will perform immunocytochemical analysis of skin biopsies and flow cytometry analysis of leukocytes in suction blisters to characterize cutaneous cellular immune processes in HIV- and HIV+ patients with secondary syphilis. Data from these studies will be correlated with our in vitro research involving immune effector cell activation by T. pallidum and treponemal lipoproteins.
In Specific Aim 2, we will use the same immunocytochemical and flow cytometric approaches to characterize the cutaneous inflammatory response to synthetic analogs (lipopeptides) of T. pallidum lipoproteins. These experiments are an outgrowth of our hypothesis that T. pallidum lipoproteins are major inflammatory mediators during syphilitic infection. Building upon our observation that T. pallidum lipoprotein analogs induce HIV gene expression in vitro, the experiments in Specific Aim 3 will elucidate the mechanisms which underlie this phenomenon. A principal long-term objective of this research is to elucidate the immune/inflammatory events during syphilitic infection which engender both clinical manifestations and protective immunity. An equally important objective is to obtain cellular and molecular data which will complement our emerging understanding of the interactions between syphilis and HIV infection, including the potential for syphilis to serve as a co-factor for HIV transmission and for HIV infection to alter the clinical course of syphilis.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR006192-07
Application #
6412407
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
1993-12-15
Project End
2003-11-30
Budget Start
Budget End
Support Year
7
Fiscal Year
2000
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Type
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030
Lieberman, Richard; Kranzler, Henry R; Levine, Eric S et al. (2018) Examining the effects of alcohol on GABAA receptor mRNA expression and function in neural cultures generated from control and alcohol dependent donor induced pluripotent stem cells. Alcohol 66:45-53
Usmani, Saad; Choquette, Linda; Bona, Robert et al. (2018) Transient bacteremia induced by dental cleaning is not associated with infection of central venous catheters in patients with cancer. Oral Surg Oral Med Oral Pathol Oral Radiol 125:286-294
Moscufo, Nicola; Wakefield, Dorothy B; Meier, Dominik S et al. (2018) Longitudinal microstructural changes of cerebral white matter and their association with mobility performance in older persons. PLoS One 13:e0194051
Santos-Cortez, Regie Lyn P; Hu, Ying; Sun, Fanyue et al. (2017) Identification of ASAH1 as a susceptibility gene for familial keloids. Eur J Hum Genet 25:1155-1161
Jin, Lingling; Liu, Yi; Sun, Fanyue et al. (2017) Three novel ANO5 missense mutations in Caucasian and Chinese families and sporadic cases with gnathodiaphyseal dysplasia. Sci Rep 7:40935
Lieberman, Richard; Kranzler, Henry R; Levine, Eric S et al. (2017) Examining FKBP5 mRNA expression in human iPSC-derived neural cells. Psychiatry Res 247:172-181
Litt, Mark D; Duffy, Valerie; Oncken, Cheryl (2016) Cigarette smoking and electronic cigarette vaping patterns as a function of e-cigarette flavourings. Tob Control 25:ii67-ii72
Rash, Carla J; Burki, Madison; Montezuma-Rusca, Jairo M et al. (2016) A retrospective and prospective analysis of trading sex for drugs or money in women substance abuse treatment patients. Drug Alcohol Depend 162:182-9
Walter, Kimberly N; Petry, Nancy M (2016) Lifetime suicide attempt history, quality of life, and objective functioning among HIV/AIDS patients with alcohol and illicit substance use disorders. Int J STD AIDS 27:476-85
Litt, Mark D; Kadden, Ronald M; Tennen, Howard et al. (2016) Network Support II: Randomized controlled trial of Network Support treatment and cognitive behavioral therapy for alcohol use disorder. Drug Alcohol Depend 165:203-12

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