Giardia lamblia is the most common protozoan cause of diarrhea in the world. It infects ~500 million people worldwide, often resulting in nutrient malabsorption which can lead to physical and cognitive developmental defects in children. Recent data suggest that the parasite is able to glycosylate secreted and surface proteins with N-acetylglucosamine and that recognition of this sugar by the mannose binding lectin (MBL) can activate the complement cascade. Our hypothesis is that recognition of parasite glycoproteins by host lectins plays a significant role in activating both innate and adaptive immune responses. We will address this specifically by examining infections in mice lacking host lectins and examining the impact on the course of infection and the innate and adaptive immune responses.

Public Health Relevance

Giardia is the most commonly diagnosed protozoan cause of diarrhea in the United States. This proposal seeks to understand how the body's immune system initially recognizes the infecting parasite and determines whether and what kind of immune response to produce. This information is essential for developing vaccines against Giardia, as well as understanding how dysregulation of intestinal immunity leads to syndromes such as celiac, disease, food allergies and Crohn's disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15AI109591-01A1
Application #
8768806
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Wali, Tonu M
Project Start
2014-07-01
Project End
2017-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Georgetown University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Washington
State
DC
Country
United States
Zip Code
20057
Coelho, Camila H; Singer, Steven M (2018) Recent advances in the Giardia-host relationship reveal danger lurking behind the smile. PLoS Negl Trop Dis 12:e0006625
Coelho, Camila Henriques; Durigan, MaurĂ­cio; Leal, Diego Averaldo Guiguet et al. (2017) Giardiasis as a neglected disease in Brazil: Systematic review of 20 years of publications. PLoS Negl Trop Dis 11:e0006005
Barash, N R; Maloney, J G; Singer, S M et al. (2017) Giardia Alters Commensal Microbial Diversity throughout the Murine Gut. Infect Immun 85:
Fink, Marc Y; Singer, Steven M (2017) The Intersection of Immune Responses, Microbiota, and Pathogenesis in Giardiasis. Trends Parasitol 33:901-913
Bartelt, Luther A; Bolick, David T; Mayneris-Perxachs, Jordi et al. (2017) Cross-modulation of pathogen-specific pathways enhances malnutrition during enteric co-infection with Giardia lamblia and enteroaggregative Escherichia coli. PLoS Pathog 13:e1006471
Nooshadokht, Maryam; Kalantari-Khandani, Behjat; Sharifi, Iraj et al. (2017) Stool antigen immunodetection for diagnosis of Giardia duodenalis infection in human subjects with HIV and cancer. J Microbiol Methods 141:35-41
Li, Erqiu; Tako, Ernest A; Singer, Steven M (2016) Complement Activation by Giardia duodenalis Parasites through the Lectin Pathway Contributes to Mast Cell Responses and Parasite Control. Infect Immun 84:1092-1099
Coelho, Camila Henriques; Costa, Adriana Oliveira; Silva, Ana Carolina Carvalho et al. (2016) Genotyping and Descriptive Proteomics of a Potential Zoonotic Canine Strain of Giardia duodenalis, Infective to Mice. PLoS One 11:e0164946
Tosh, Kevin W; Mittereder, Lara; Bonne-Annee, Sandra et al. (2016) The IL-12 Response of Primary Human Dendritic Cells and Monocytes to Toxoplasma gondii Is Stimulated by Phagocytosis of Live Parasites Rather Than Host Cell Invasion. J Immunol 196:345-56
Keselman, Aleksander; Li, Erqiu; Maloney, Jenny et al. (2016) The Microbiota Contributes to CD8+ T Cell Activation and Nutrient Malabsorption following Intestinal Infection with Giardia duodenalis. Infect Immun 84:2853-60

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