This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In contrast to HIV infection in humans, natural SIV infections of African nonhuman primates are typically non-pathogenic despite similarly high virus replication. While the mechanisms underlying this strikingly different outcome are still largely unknown, a consistent feature of natural SIV infections is the lack of chronic immune activation. In HIV-infected humans, loss of mucosal immunity and microbial translocation from the intestinal lumen to the systemic circulation contribute to chronic immune activation and disease progression. Recently, we have shown that pathogenic HIV and SIV infections of humans and rhesus macaques (RMs) are associated with preferential depletion of mucosal CD4+ Th17 cells, a T helper cell population critical for the maintenance of mucosal barrier integrity and production of anti-microbial molecules. Remarkably, this depletion of mucosal Th17 cells is not observed during natural, nonpathogenic SIV infection of sooty mangabeys (SMs), a natural host species.
The Aim of this project is to identify mechanism(s) responsible for the regulation of mucosal Th17 cells in pathogenic and nonpathogenic infections. We will test the following hypotheses to explain why Th17 cells are preserved in SIV-infected SMs but not in HIV-infected humans or SIV-infected RMs: (i) Th17 cells are more resistant to virus infection [Aim 1];(ii) Th17 cell renewal and/or differentiation are more effective in maintaining Th17 homeostasis [Aim 2];(iii) Th17 cell homing to mucosal tissues is better preserved [Aim 3]. We believe that this information will be relevant to the design of an AIDS vaccine that will confer protection from the HIV-associated mucosal immune dysfunction.
|Maddox, S A; Kilaru, V; Shin, J et al. (2017) Estrogen-dependent association of HDAC4 with fear in female mice and women with PTSD. Mol Psychiatry :|
|Banerjee, Sunayana B; Gutzeit, Vanessa A; Baman, Justin et al. (2017) Perineuronal Nets in the Adult Sensory Cortex Are Necessary for Fear Learning. Neuron 95:169-179.e3|
|Bruner, Emiliano; Preuss, Todd M; Chen, Xu et al. (2017) Evidence for expansion of the precuneus in human evolution. Brain Struct Funct 222:1053-1060|
|Chen, Guiqin; Nie, Shuke; Han, Chao et al. (2017) Antidyskinetic Effects of MEK Inhibitor Are Associated with Multiple Neurochemical Alterations in the Striatum of Hemiparkinsonian Rats. Front Neurosci 11:112|
|Dehkharghani, S; Fleischer, C C; Qiu, D et al. (2017) Cerebral Temperature Dysregulation: MR Thermographic Monitoring in a Nonhuman Primate Study of Acute Ischemic Stroke. AJNR Am J Neuroradiol 38:712-720|
|Walker, Lary C; Jucker, Mathias (2017) The Exceptional Vulnerability of Humans to Alzheimer's Disease. Trends Mol Med 23:534-545|
|Payne, Christa; Cirilli, Laetitia; Bachevalier, Jocelyne (2017) An MRI study of the corpus callosum in monkeys: Developmental trajectories and effects of neonatal hippocampal and amygdala lesions. Dev Psychobiol 59:495-506|
|Tedesco, Dana; Thapa, Manoj; Gumber, Sanjeev et al. (2017) CD4(+) Foxp3(+) T cells promote aberrant immunoglobulin G production and maintain CD8(+) T-cell suppression during chronic liver disease. Hepatology 65:661-677|
|Hecht, E E; Mahovetz, L M; Preuss, T M et al. (2017) A neuroanatomical predictor of mirror self-recognition in chimpanzees. Soc Cogn Affect Neurosci 12:37-48|
|Fonseca, Jairo A; McCaffery, Jessica N; Kashentseva, Elena et al. (2017) A prime-boost immunization regimen based on a simian adenovirus 36 vectored multi-stage malaria vaccine induces protective immunity in mice. Vaccine 35:3239-3248|
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