Abstract

Ascaris spp. infection affects 800 million people worldwide, and half of the world population is currently at risk of infection. Recurrent reinfection in humans is mostly due to the simplicity of the parasite life cycle, but the impact of multiple exposures to the biology of the infection and the consequences to the host’s homeostasis are poorly understood. In this context, single and multiple exposures in mice were performed in order to characterize the parasitological, histopathological, tissue functional and immunological aspects of experimental larval ascariasis. The most important findings revealed that reinfected mice presented a significant reduction of parasite burden in the lung and an increase in the cellularity in the bronchoalveolar lavage (BAL) associated with a robust granulocytic pulmonary inflammation, leading to a severe impairment of respiratory function. Moreover, the multiple exposures to Ascaris elicited an increased number of circulating inflammatory cells as well as production of higher levels of systemic cytokines, mainly IL-4, IL-5, IL-6, IL-10, IL-17A and TNF-α when compared to single-infected animals. Taken together, our results suggest the intense pulmonary inflammation associated with a polarized systemic Th2/Th17 immune response are crucial to control larval migration after multiple exposures to Ascaris.

Highlights

  • New information from the Global Burden of Disease Study 2010 (GBD 2010) indicates that more than 800 million people are infected with Ascaris spp. (A. lumbricoides and A. suum), which ranks ascariasis as the most common affliction of people living in poverty [1]

  • Human ascariasis caused by the helminths Ascaris lumbricoides and Ascaris suum, is the most prevalent neglected tropical disease in the world, affecting more than 800 million

  • Based on a previous study from our group, we sought to determine whether multiple exposures to A. suum influenced the number of larvae recovered from liver, lung and small intestine

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Summary

Introduction

New information from the Global Burden of Disease Study 2010 (GBD 2010) indicates that more than 800 million people are infected with Ascaris spp. (A. lumbricoides and A. suum), which ranks ascariasis as the most common affliction of people living in poverty [1]. New information from the Global Burden of Disease Study 2010 (GBD 2010) indicates that more than 800 million people are infected with Ascaris spp. A. suum has been implicated as an anthropozoonotic species based on epidemiological evidence from the field [2], molecular similarity to A. lumbricoides [3, 4] and by experimental infection in humans [5]. Despite the lack of evidence on Ascaris infection, new studies have been proposed that an IL-6-dependent, Th17 response might play an important role into the pathogenesis of helminth infections [11] and allergic manifestations [12], resulting in modulation of the Th2 response and possible susceptibility of the host to the parasitic infection. The role of IL-17 in the pathogenesis of helminth infection was highlighted in the development of hepatointestinalperioval granulomas caused by Schistosoma mansoni infection [13]

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