The purpose of this study was to examine the potential of developing a primate model of vaginal candidiasis. Mucosal candidiasis is very common in immunocompromised individuals and is caused by Candida species, especially C. albicans. C. albicans is a commensal organism of the human intestinal and reproductive tracts and thus health individuals have demonstrable Candida-specific cell-mediated and humoral immunity. Susceptibility to mucosal candidiasis is thought to involve a dysfunction in this normal protective immunity. Protective host defense mechanisms functioning at the vaginal mucosa are poorly understood and animal models are currently being used to better understand both local and systemic immunity in response to C. albicans vaginal infection. Currently, animal models of vaginal candidiasis have been restricted to rodents (mice and rats). However, rodents are not normally colonized with C. albicans or any yeast and thus do not have the demonstrable humoral and cell-mediated immunity against C. albicans that humans have. This unfortunate circumstance makes comparison to the human disease difficult. The circumvent this, we examined whether rhesus and pigtailed macaques were asymptomatically colonized with yeast, had demonstrable Candida-specific cell-mediated immunity (proliferation of peripheral blood lymphocytes in response to Candida antigen), and could acquire an experimental vaginal C. albicans infection. Results shows that indeed both pigailed and rhesus macaques were colonized vaginally with yeast and had positive peripheral blood lymphocyte responses to C. albicans antigens. Cytokines and Candida-specific antibodies were detected in vaginal lavage fluid, the cytokines showing a Th2-type profile with high levels of IL-4 and IL-10 together with lower levels of IL-2 and IFN- . Also, epithelial cells collected from vaginal lavages of both species inhibited the growth of C. albicans in vitro similar to mouse and human vaginal epithelial cells. Interestingly, the rhesus, but not pigtailed macaques were susceptible to experimental vaginitis. This was true in untreated conditions, after reduction of normal vaginal flora, and after induction of pseudoestrus (required in rodents to establish an infection). Also of interest was the reduced vaginal epithelial cell-mediated anti-Candida activity in rhesus, but not pigtailed macaques, under pseudoestrus conditions. Thus, a very interesting differential susceptibility to experimental vaginal candidiasis has been observed in two species of macaques that may be extremely useful to understand host defense

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
2P51RR000164-37
Application #
6277454
Study Section
Project Start
1998-09-30
Project End
1999-04-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
37
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Tulane University
Department
Type
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Mahalingam, Ravi; Kaufer, Benedikt B; Ouwendijk, Werner J D et al. (2018) Attenuation of Simian Varicella Virus Infection by Enhanced Green Fluorescent Protein in Rhesus Macaques. J Virol 92:
Kumar, Vinay; Mansfield, Joshua; Fan, Rong et al. (2018) miR-130a and miR-212 Disrupt the Intestinal Epithelial Barrier through Modulation of PPAR? and Occludin Expression in Chronic Simian Immunodeficiency Virus-Infected Rhesus Macaques. J Immunol 200:2677-2689
Parthasarathy, Geetha; Philipp, Mario T (2018) Intracellular TLR7 is activated in human oligodendrocytes in response to Borrelia burgdorferi exposure. Neurosci Lett 671:38-42
McNamara, Ryan P; Costantini, Lindsey M; Myers, T Alix et al. (2018) Nef Secretion into Extracellular Vesicles or Exosomes Is Conserved across Human and Simian Immunodeficiency Viruses. MBio 9:
Calenda, Giulia; Villegas, Guillermo; Barnable, Patrick et al. (2017) MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa. J Acquir Immune Defic Syndr 74:e67-e74
Datta, Dibyadyuti; Bansal, Geetha P; Grasperge, Brooke et al. (2017) Comparative functional potency of DNA vaccines encoding Plasmodium falciparum transmission blocking target antigens Pfs48/45 and Pfs25 administered alone or in combination by in vivo electroporation in rhesus macaques. Vaccine 35:7049-7056
Yi, Fei; Guo, Jia; Dabbagh, Deemah et al. (2017) Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1. J Virol 91:
Jorgensen, Matthew J; Lambert, Kelsey R; Breaux, Sarah D et al. (2017) Pair housing of Vervets/African Green Monkeys for biomedical research. Am J Primatol 79:1-10
Ramesh, Geeta; Martinez, Alejandra N; Martin, Dale S et al. (2017) Effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in glial and neuronal cells of the central nervous system. J Neuroinflammation 14:28
Parthasarathy, Geetha; Philipp, Mario T (2017) Receptor tyrosine kinases play a significant role in human oligodendrocyte inflammation and cell death associated with the Lyme disease bacterium Borrelia burgdorferi. J Neuroinflammation 14:110

Showing the most recent 10 out of 352 publications