Impact of Paracoccidioides brasiliensis Coinfection on the Evolution of Schistosoma mansoni- Induced Granulomatous Liver Injury in Mice

Biomed Res Int. 2019 Mar 24:2019:8319465. doi: 10.1155/2019/8319465. eCollection 2019.

Abstract

The pathogens Schistosoma mansoni and Paracoccidioides brasiliensis share common geographic areas, determining infectious diseases with high mortality rates worldwide. Histopathological and immunological changes induced by each pathogen are well understood; however, the host responses to S. mansoni and P. brasiliensis coinfection are still unknown. Thus, we investigated liver damage and cytokines production in a murine model acutely and chronically coinfected with these pathogens. Fourty male Swiss mice were infected with S. mansoni and P. brasiliensis alone or coinfected. The animals were euthanized with 50 (acute infection) and 120 (chronic infection) days of infection. All infected animals exhibited liver inflammation. Intense granulomatous inflammation was detected in animals infected with S. mansoni alone and those coinfected. Productive and involutive granulomas were clearly observed in acute and chronic infections, respectively. Granuloma size was reduced in the acute phase and increased in the chronic phase of S. mansoni and P. brasiliensis coinfection, compared with animals infected only with S. mansoni. In the chronic phase of infection, the granulomatous inflammation in coinfected animals was characterized by intense neutrophils accumulation and reduced eosinophils number. IFN-γ, IL-2, IL-4, and IL-5 circulating levels were increased in all infected groups. Coinfected animals presented attenuated IFN-γ and IL-4 production in the acute and chronic infections. Taken together, our findings indicate that coinfected animals exhibited a differential modulation of granulomatous inflammation during the acute and chronic phases of infection, which was potentially associated with a divergent profile of cytokines production and migration of neutrophils and eosinophils in response to S. mansoni and P. brasiliensis antigenic stimulation.

MeSH terms

  • Animals
  • Coinfection* / immunology
  • Coinfection* / microbiology
  • Coinfection* / parasitology
  • Coinfection* / pathology
  • Disease Models, Animal
  • Granuloma* / immunology
  • Granuloma* / microbiology
  • Granuloma* / parasitology
  • Granuloma* / pathology
  • Liver Diseases* / immunology
  • Liver Diseases* / microbiology
  • Liver Diseases* / parasitology
  • Liver Diseases* / pathology
  • Liver* / immunology
  • Liver* / microbiology
  • Liver* / parasitology
  • Liver* / pathology
  • Male
  • Mice
  • Paracoccidioides / immunology*
  • Paracoccidioidomycosis* / immunology
  • Paracoccidioidomycosis* / microbiology
  • Paracoccidioidomycosis* / pathology
  • Paracoccidioidomycosis* / physiopathology
  • Schistosoma mansoni / immunology*
  • Schistosomiasis mansoni* / immunology
  • Schistosomiasis mansoni* / microbiology
  • Schistosomiasis mansoni* / pathology