Multiple Exposures to Ascaris suum Induce Tissue Injury and Mixed Th2/Th17 Immune Response in Mice

PLoS Negl Trop Dis. 2016 Jan 27;10(1):e0004382. doi: 10.1371/journal.pntd.0004382. eCollection 2016 Jan.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascariasis / immunology*
  • Ascariasis / parasitology
  • Ascaris suum / immunology*
  • Ascaris suum / physiology
  • Cytokines / immunology
  • Female
  • Humans
  • Lung / immunology
  • Lung / parasitology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Th17 Cells / immunology*
  • Th2 Cells / immunology*

Substances

  • Cytokines

Grants and funding

This work was financially supported by the Fundação de Amparo a Pesquisa do Estado de Minas Gerais/FAPEMIG, Brazil (Grant# CBB APQ-01202-09 and Grant# CBB – PPM-00296-11), the Brazilian National Research Council (CNPq) (Grant# 478729/ 2011-1 and Grant# 470613/2012-5), Pró-Reitoria de Pesquisa of Universidade Federal de Minas Gerais and CAPES. RTF and PHGG are supported by CNPq fellowships. DSN is supported by CAPES fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.