1887

Abstract

The outcome of infection is strongly influenced by the host’s genetic background. BALB/c mice are susceptible to infection, while C57BL/6 mice show discrete resistance. Central to the fate of the infection is the availability of -arginine and the related metabolic processes in the host and parasite. Depending on -arginine availability, nitric oxide synthase 2 (NOS2) of the host cell produces nitric oxide (NO) controlling the parasite growth. On the other hand, can also use host -arginine for the production of polyamines through its own arginase activity, thus favouring parasite replication. Considering RNA-seq data, we analysed the dual modulation of host and parasite gene expression of BALB/c or C57BL/6 mouse bone marrow-derived macrophages (BMDMs) after 4 h of infection with wild-type (-WT) or arginase knockout (-arg). We identified 12 641 host transcripts and 8282 parasite transcripts by alignment analysis with the respective and genomes. The comparison of BALB/c_-arg BALB/c_-WT revealed 233 modulated transcripts, with most related to the immune response and some related to the amino acid transporters and -arginine metabolism. In contrast, the comparison of C57BL/6_-arg C57BL/6_-WT revealed only 30 modulated transcripts, including some related to the immune response but none related to amino acid transport or -arginine metabolism. The transcriptome profiles of the intracellular amastigote revealed 94 modulated transcripts in the comparison of -arg_BALB/c -WT_BALB/c and 45 modulated transcripts in the comparison of -arg_C57BL/6 -WT_C57BL/6. Taken together, our data present new insights into the impact of parasite arginase activity on the orchestration of the host gene expression modulation, including in the immune response and amino acid transport and metabolism, mainly in susceptible BALB/c-infected macrophages. Moreover, we show how parasite arginase activity affects parasite gene expression modulation, including amino acid uptake and amastin expression.

Funding
This study was supported by the:
  • Audun Helge Nerland , Universitetet i Bergen
  • Karl Erik Müller , Universitetet i Bergen
  • Audun Helge Nerland , Senter for Internasjonalisering av Utdanning
  • Karl Erik Müller , Senter for Internasjonalisering av Utdanning
  • Juliana ide Aoki , Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
  • Lucile Maria Floeter-Winter , Conselho Nacional de Desenvolvimento Científico e Tecnológico , (Award 308667/2018-2)
  • Sandra Marcia Muxel , Conselho Nacional de Desenvolvimento Científico e Tecnológico , (Award 406351/2018-0)
  • Lucile Maria Floeter-Winter , Fundação de Amparo à Pesquisa do Estado de São Paulo , (Award #2018/23512-0 and #2014/50717-1)
  • Maria Fernanda Laranjeira-Silva , Fundação de Amparo à Pesquisa do Estado de São Paulo , (Award #2017/23933-3)
  • Sandra Marcia Muxel , Fundação de Amparo à Pesquisa do Estado de São Paulo , (Award #2018/24693-9)
  • Juliana ide Aoki , Fundação de Amparo à Pesquisa do Estado de São Paulo (BR) , (Award #2016/03273-6)
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2020-09-04
2020-12-01
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