PMID- 32886592
OWN - NLM
STAT- MEDLINE
DCOM- 20210816
LR  - 20231214
IS  - 2057-5858 (Electronic)
IS  - 2057-5858 (Linking)
VI  - 6
IP  - 9
DP  - 2020 Sep
TI  - Dual transcriptome analysis reveals differential gene expression modulation 
      influenced by Leishmania arginase and host genetic background.
LID - 10.1099/mgen.0.000427 [doi]
LID - mgen000427
AB  - The outcome of Leishmania infection is strongly influenced by the host's genetic 
      background. BALB/c mice are susceptible to Leishmania infection, while C57BL/6 
      mice show discrete resistance. Central to the fate of the infection is the 
      availability of l-arginine and the related metabolic processes in the host and 
      parasite. Depending on l-arginine availability, nitric oxide synthase 2 (NOS2) of 
      the host cell produces nitric oxide (NO) controlling the parasite growth. On the 
      other hand, Leishmania can also use host l-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 Leishmania amazonensis wild-type 
      (La-WT) or L. amazonensis arginase knockout (La-arg(-)). We identified 12 641 
      host transcripts and 8282 parasite transcripts by alignment analysis with the 
      respective Mus musculus and L. mexicana genomes. The comparison of 
      BALB/c_La-arg(-)versus BALB/c_La-WT revealed 233 modulated transcripts, with most 
      related to the immune response and some related to the amino acid transporters 
      and l-arginine metabolism. In contrast, the comparison of C57BL/6_La-arg(-)vs. 
      C57BL/6_La-WT revealed only 30 modulated transcripts, including some related to 
      the immune response but none related to amino acid transport or l-arginine 
      metabolism. The transcriptome profiles of the intracellular amastigote revealed 
      94 modulated transcripts in the comparison of La-arg(-)_BALB/c vs. La-WT_BALB/c 
      and 45 modulated transcripts in the comparison of La-arg(-)_C57BL/6 vs. 
      La-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.
FAU - Aoki, Juliana Ide
AU  - Aoki JI
AD  - Department of Physiology, Institute of Bioscience, University of Sao Paulo, Sao 
      Paulo, Brazil.
FAU - Muxel, Sandra Marcia
AU  - Muxel SM
AD  - Department of Physiology, Institute of Bioscience, University of Sao Paulo, Sao 
      Paulo, Brazil.
FAU - Laranjeira-Silva, Maria Fernanda
AU  - Laranjeira-Silva MF
AD  - Department of Physiology, Institute of Bioscience, University of Sao Paulo, Sao 
      Paulo, Brazil.
FAU - Zampieri, Ricardo Andrade
AU  - Zampieri RA
AD  - Department of Physiology, Institute of Bioscience, University of Sao Paulo, Sao 
      Paulo, Brazil.
FAU - Muller, Karl Erik
AU  - Muller KE
AD  - Department of Clinical Science, University of Bergen, Bergen, Norway.
AD  - Department of Internal Medicine, Drammen Hospital, Drammen, Norway.
FAU - Nerland, Audun Helge
AU  - Nerland AH
AD  - Department of Clinical Science, University of Bergen, Bergen, Norway.
FAU - Floeter-Winter, Lucile Maria
AU  - Floeter-Winter LM
AD  - Department of Physiology, Institute of Bioscience, University of Sao Paulo, Sao 
      Paulo, Brazil.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200904
PL  - England
TA  - Microb Genom
JT  - Microbial genomics
JID - 101671820
RN  - 0 (Protozoan Proteins)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - EC 3.5.3.1 (Arginase)
SB  - IM
MH  - Animals
MH  - Arginase/*genetics
MH  - Female
MH  - Gene Expression Profiling/*methods
MH  - Gene Expression Regulation
MH  - Genetic Background
MH  - High-Throughput Nucleotide Sequencing
MH  - Leishmania/*genetics
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Nitric Oxide Synthase Type II/*genetics
MH  - Protozoan Proteins/genetics
MH  - Sequence Analysis, RNA
PMC - PMC7643972
OTO - NOTNLM
OT  - BALB/c
OT  - C57BL/6
OT  - Leishmania amazonensis
OT  - RNA-seq
OT  - arginine transport
OT  - immune response
OT  - macrophage infection
COIS- The authors declare that there are no conflicts of interest.
EDAT- 2020/09/05 06:00
MHDA- 2021/08/17 06:00
PMCR- 2020/09/04
CRDT- 2020/09/04 17:09
PHST- 2020/09/05 06:00 [pubmed]
PHST- 2021/08/17 06:00 [medline]
PHST- 2020/09/04 17:09 [entrez]
PHST- 2020/09/04 00:00 [pmc-release]
AID - 000427 [pii]
AID - 10.1099/mgen.0.000427 [doi]
PST - ppublish
SO  - Microb Genom. 2020 Sep;6(9):mgen000427. doi: 10.1099/mgen.0.000427. Epub 2020 Sep 
      4.