Cellular immune responses in peripheral blood lymphocytes of Giardia infected squirrel monkey (Saimiri boliviensis boliviensis) treated with Fenbendazole

• Published in: PloS one Vol. 13; no. 11; p. e0198497
• Main Authors: Nehete, Pramod N, Wilkerson, Gregory, Nehete, Bharti P, Chitta, Sriram, Ruiz, Julio C, Scholtzova, Henrieta, Williams, Lawrence E, Abee, Christian R, Vanchiere, John A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.11.2018; Public Library of Science (PLoS)
• Subjects: Animals; Antinematodal Agents - pharmacology; Antinematodal Agents - therapeutic use; Biology and Life Sciences; Blood; Breeding of animals; Cancer; CD14 antigen; CD16 antigen; Cell surface; Concanavalin A; Cytokines; Cytokines - blood; Enzyme-linked immunosorbent assay; Eosinophils; Erythrocytes; Fenbendazole - pharmacology; Fenbendazole - therapeutic use; Flow cytometry; Giardia; Giardiasis - drug therapy; Giardiasis - immunology; Giardiasis - veterinary; Hematocrit; Hemoglobin; Immune response; Immune response (cell-mediated); Immune system; Immunity, Cellular - drug effects; Immunology; Infections; Interleukin 1 receptor antagonist; Interleukin 1 receptors; Interleukin 10; Interleukin 12; Interleukin 13; Interleukin 4; Interleukin 6; Laboratory animals; Leukocytes; Leukocytes (eosinophilic); Leukocytes (neutrophilic); Lipopolysaccharides; Lymphocytes; Lymphocytes - drug effects; Lymphocytes - immunology; Lymphocytes B; Mammals; Medical research; Medicine and Health Sciences; Monkeys; Monocytes; Parasites; Parasitic diseases; Peripheral blood; Research and Analysis Methods; Saimiri; Sciuridae - immunology; Stimulation; Surface markers; γ-Interferon; Louisiana; New York; United States > US; Texas
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0198497

Cellular immune responses were tested to determine the effect of fenbendazole on the function of lymphocytes from Bolivian squirrel monkeys (Samiri boliviensis boliviensis). Giardia-infected squirrel monkeys were treated with commercially available fenbendazole (FBZ)-medicated monkey chow. Immune responses were compared between historical controls (Giardia naïve, untreated with FBZ (control animals)) and Giardia-infected, FBZ-treated squirrel monkeys (study animals). Peripheral blood lymphocytes from study monkeys had significantly lower stimulation indices compared to control animals when cultured in vitro with concanavalin A (Con A) (p<0.0001), phytohaemagglutinin (PHA) (p<0.0001) and lipopolysaccharide (LPS) (p<0.0001). PBMCs were also analyzed for IFN-γ producing cells in response to stimulation with Con A, PHA, PWM, and LPS by the cytokine ELISPOT assay. Significantly higher responses to Con A- (p<0.0001), and PHA- (p<0.001) stimulated cultures from Giardia-infected and fenbendazole treated compared to controls. Flow cytometric analysis for expression of cell surface markers revealed a significant increase in B- and NKT-lymphocytes and significant decrease in CD14+CD16+ monocytes after FBZ treatment. Also, circulating plasma cytokines IFN-γ, TNF-α, IL-12p40, IL-1β, IL-10, IL-13, IL-1ra, IL-6 and IL-4 were significantly decreased after FBZ treatment. Comparison of hematologic parameters between controls and FBZ-treated squirrel monkeys revealed significantly lower numbers of total leukocytes, neutrophils, monocytes, and eosinophils compared to controls. However, erythrocyte indices (red cell count, hemoglobin and hematocrit were significantly higher in FBZ-treated monkeys. Our findings suggest that fenbendazole treatment may alter sensitive immune and molecular measures of inflammation. Postponing the experimental use of squirrel monkeys until at least 6 weeks after FBZ treatment should be considered.