Characterization of the immune response in a murine model of Mycobacterium tuberculosis H37Rv coinfection with Taenia crassiceps.

• ¹ Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", Neuropatología, Mexico
• ² Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Patología Experimental, Mexico
• ³ Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", Neuropsicofarmacología, Mexico
• ⁴ Instituto Politécnico Nacional, Escuela Superior de Medicina, Mexico
• ⁵ Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Mexico
• ⁶ Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Patología, Mexico

Introduction: In Mexico, helminthiasis remains as one of the 20 main causes of morbidity. It is considered that at least a 45% of the population is infested. The helminths modify the host’s immune response. They induce a Th2 lymphocyte profile due to T helper cells recruitment. In this event, an important reduction in Th1 lymphocyte activation is observed, making inefficient the immune response against intracellular pathogens such as mycobacterium. Nowadays, helminths are not considered as a risk factor to introduce other comorbidities; however, they are linked to immunosuppression, situation that conditions diverse pathologies such as tuberculosis. Objective: To determine the immunologic characteristics of the coinfection of Taenia crassiceps and Mycobacterium tuberculosis in an experimental murine model and to make a histopathological evaluation of this model. Material and methods: It is an experimental, longitudinal and prospective study. Balb/c strain male mice of 6 to 8 weeks of age were separated into 3 groups. Group 1 was infected intratracheally with 250 000 mycobacterium of the H37Rv strain, group 2 was infested intraperitoneally with 15 cysticercus of Taenia crassiceps ORF strain, group 3 was inoculated with cysticercus and subdivided into 7 subgroups, that were coinfected with Mycobacterium tuberculosis at the 1st, 3rd, 7th, 14th, 21st, 24th and 55th days following infection with Taenia crassiceps. From each group, 4 mice were sacrificed at day 55 during coinfection; serum cytokines (IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-2, IL 17) were quantified by flow cytometry as well as H and E histopathology analysis in lungs. Results: In group 1 the Th1 cytokine pattern was dynamic, whereas, the Th2 profile reached its peak at day 10. We found anatomopathological evidence of pulmonary tuberculosis starting on day 14, showing vasculitis, pneumonia, edema and well defined granulomas. In group 2 a Th1 cytokine profile was observed during the first 55 days of the infection and posteriorly a marked Th2 profile was observed until the end of the experiment. The histologic analysis found out that in this group the lungs showed no alteration, but evidence of Taenia crassiceps infestation was found. For the coinfected animal group the Th1 cytokine profile showed no expression pattern and the Th2 predominated only in the coinfected groups at days 21 and 55. In all the samples extensive inflammatory infiltrate, edema, vasculitis and granulomas were observed. In early stages of the coinfected group there was no significant difference in the CFU numbers in comparison to the control group. Discussion: Infestation by Taenia crassiceps is immune response modulating factor in the host that alters cytokine expression, which translates in a modified tuberculosis infection development. Conclusion: Helminthiasis modulates the host immune response and conditions the establishment and development of tuberculosis.