This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chancroid, a genital ulcer disease common caused by Haemophilus ducreyi, is common in several developing countries where it is associated with the heterosexual transmission of HIV. In the United States, chancroid is associated with endemics in populations at high risk for HIV infection. The goal of this project is to understand the mechanisms by which H. ducreyi causes disease, a finding that would allow scientists to devise vaccines and other strategies for prevention. We hypothesize that two toxins produced by H. ducreyi are important in the ability of this organism to damage host tissue, evade the host immune response, and persist in infected individuals. To explore this hypothesis, we are studying the specific immune response to H. ducreyi in primates infected with this organism. In addition, we are comparing the ability of two H. ducreyi strains, one that produces toxins and one that does not, to cause ulcers and survive in the primate model of infection. In the past year, we had completed our construction of a mutant strain of H. ducreyi lacking the two toxins, inoculated this mutant as well as the wild type strain into four primates and found that the mutant was defective in survival in resulting lesions. We subsequently repaired the defect in the mutant and are currently determining whether virulence is restored, hopefully confirming that the mutant's decreased survival was due solely to the toxin genes and not another fortuitous mutation. These experiments are particularly significant, given that experiments with similar mutants in other animal models showed no effect, possibly reflecting the host specificity for these toxins. Finally, we are completing our analysis of the humoral antibody response (detectable, but lower than expected), local cytokines induced by infection (IFNgamma gt IL4), and the cellular infiltration induced by infection.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000166-45
Application #
7349384
Study Section
Special Emphasis Panel (ZRR1-CM-9 (01))
Project Start
2006-05-01
Project End
2007-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
45
Fiscal Year
2006
Total Cost
$228,467
Indirect Cost
Name
University of Washington
Department
Veterinary Sciences
Type
Other Domestic Higher Education
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Pham, Amelie; Carrasco, Marisa; Kiorpes, Lynne (2018) Endogenous attention improves perception in amblyopic macaques. J Vis 18:11
Zanos, Stavros; Rembado, Irene; Chen, Daofen et al. (2018) Phase-Locked Stimulation during Cortical Beta Oscillations Produces Bidirectional Synaptic Plasticity in Awake Monkeys. Curr Biol 28:2515-2526.e4
Choi, Hannah; Pasupathy, Anitha; Shea-Brown, Eric (2018) Predictive Coding in Area V4: Dynamic Shape Discrimination under Partial Occlusion. Neural Comput 30:1209-1257
Shushruth, S; Mazurek, Mark; Shadlen, Michael N (2018) Comparison of Decision-Related Signals in Sensory and Motor Preparatory Responses of Neurons in Area LIP. J Neurosci 38:6350-6365
Raghanti, Mary Ann; Edler, Melissa K; Stephenson, Alexa R et al. (2018) A neurochemical hypothesis for the origin of hominids. Proc Natl Acad Sci U S A 115:E1108-E1116
Wool, Lauren E; Crook, Joanna D; Troy, John B et al. (2018) Nonselective Wiring Accounts for Red-Green Opponency in Midget Ganglion Cells of the Primate Retina. J Neurosci 38:1520-1540
Hasegawa, Yu; Curtis, Britni; Yutuc, Vernon et al. (2018) Microbial structure and function in infant and juvenile rhesus macaques are primarily affected by age, not vaccination status. Sci Rep 8:15867
Oleskiw, Timothy D; Nowack, Amy; Pasupathy, Anitha (2018) Joint coding of shape and blur in area V4. Nat Commun 9:466
Klegarth, Amy R; Ezeonwu, Chigozie A; Rompis, Aida et al. (2017) Survey of Treponemal Infections in Free-Ranging and Captive Macaques, 1999-2012. Emerg Infect Dis 23:816-819
Hallum, Luke E; Shooner, Christopher; Kumbhani, Romesh D et al. (2017) Altered Balance of Receptive Field Excitation and Suppression in Visual Cortex of Amblyopic Macaque Monkeys. J Neurosci 37:8216-8226

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