PMID- 36581764
OWN - NLM
STAT- MEDLINE
DCOM- 20230106
LR  - 20230124
IS  - 2399-3642 (Electronic)
IS  - 2399-3642 (Linking)
VI  - 5
IP  - 1
DP  - 2022 Dec 29
TI  - Axl receptor induces efferocytosis, dampens M1 macrophage responses and promotes 
      heart pathology in Trypanosoma cruzi infection.
PG  - 1421
LID - 10.1038/s42003-022-04401-w [doi]
LID - 1421
AB  - Adaptive immunity controls Trypanosoma cruzi infection, but the protozoan 
      parasite persists and causes Chagas disease. T cells undergo apoptosis, and the 
      efferocytosis of apoptotic cells might suppress macrophages and exacerbate 
      parasite infection. Nonetheless, the receptors involved in the efferocytosis of 
      apoptotic lymphocytes during infection remain unknow. Macrophages phagocytose 
      apoptotic cells by using the TAM (Tyro3, Axl, Mer) family of receptors. To 
      address how the efferocytosis of apoptotic cells affects macrophage-mediated 
      immunity, we employ here Axl receptor- and Mer receptor-deficient mouse strains. 
      In bone marrow-derived macrophages (BMDMs), both Axl and Mer receptors play a 
      role in the efferocytosis of proapoptotic T cells from T. cruzi-infected mice. 
      Moreover, treatment with a TAM receptor inhibitor blocks efferocytosis and 
      upregulates M1 hallmarks induced by immune T cells from infected mice. 
      Remarkably, the use of Axl(-/-) but not Mer(-/-) macrophages increases 
      T-cell-induced M1 responses, such as nitric oxide production and control of 
      parasite infection. Furthermore, infected Axl(-/-) mice show reduced peak 
      parasitemia, defective efferocytosis, improved M1 responses, and ameliorated 
      cardiac inflammation and fibrosis. Therefore, Axl induces efferocytosis, disrupts 
      M1 responses, and promotes parasite infection and pathology in experimental 
      Chagas disease. Axl stands as a potential host-direct target for switching 
      macrophage phenotypes in infectious diseases.
CI  - (c) 2022. The Author(s).
FAU - Rigoni, Thais S
AU  - Rigoni TS
AD  - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de 
      Janeiro, Rio de Janeiro, RJ, Brazil.
FAU - Vellozo, Natalia S
AU  - Vellozo NS
AUID- ORCID: 0000-0001-9988-5635
AD  - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de 
      Janeiro, Rio de Janeiro, RJ, Brazil.
FAU - Guimaraes-Pinto, Kamila
AU  - Guimaraes-Pinto K
AUID- ORCID: 0000-0003-2642-5229
AD  - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de 
      Janeiro, Rio de Janeiro, RJ, Brazil.
AD  - Instituto de Microbiologia Paulo de Goes, Universidade Federal do Rio de Janeiro, 
      Rio de Janeiro, RJ, Brazil.
FAU - Cabral-Piccin, Mariela
AU  - Cabral-Piccin M
AD  - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de 
      Janeiro, Rio de Janeiro, RJ, Brazil.
FAU - Fabiano-Coelho, Laryssa
AU  - Fabiano-Coelho L
AUID- ORCID: 0000-0002-1853-5930
AD  - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de 
      Janeiro, Rio de Janeiro, RJ, Brazil.
FAU - Matos-Silva, Thayane C
AU  - Matos-Silva TC
AUID- ORCID: 0000-0001-8903-4124
AD  - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de 
      Janeiro, Rio de Janeiro, RJ, Brazil.
FAU - Filardy, Alessandra A
AU  - Filardy AA
AUID- ORCID: 0000-0003-4098-3235
AD  - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de 
      Janeiro, Rio de Janeiro, RJ, Brazil.
AD  - Instituto de Microbiologia Paulo de Goes, Universidade Federal do Rio de Janeiro, 
      Rio de Janeiro, RJ, Brazil.
FAU - Takiya, Christina M
AU  - Takiya CM
AUID- ORCID: 0000-0002-8019-628X
AD  - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de 
      Janeiro, Rio de Janeiro, RJ, Brazil.
FAU - Lopes, Marcela F
AU  - Lopes MF
AUID- ORCID: 0000-0002-4508-0505
AD  - Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de 
      Janeiro, Rio de Janeiro, RJ, Brazil. marcelal@biof.ufrj.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221229
PL  - England
TA  - Commun Biol
JT  - Communications biology
JID - 101719179
RN  - 0 (Carrier Proteins)
RN  - 0 (AXL receptor tyrosine kinase, mouse)
RN  - 0 (Axl Receptor Tyrosine Kinase)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Carrier Proteins
MH  - *Chagas Disease/immunology/pathology
MH  - *Macrophages
MH  - Phagocytosis
MH  - Mice, Knockout
MH  - *Axl Receptor Tyrosine Kinase/genetics
MH  - Heart/parasitology
MH  - *Myocardium/pathology
PMC - PMC9800583
COIS- The authors declare no competing interests.
EDAT- 2022/12/30 06:00
MHDA- 2023/01/03 06:00
PMCR- 2022/12/29
CRDT- 2022/12/29 23:29
PHST- 2022/11/11 00:00 [received]
PHST- 2022/12/22 00:00 [accepted]
PHST- 2022/12/29 23:29 [entrez]
PHST- 2022/12/30 06:00 [pubmed]
PHST- 2023/01/03 06:00 [medline]
PHST- 2022/12/29 00:00 [pmc-release]
AID - 10.1038/s42003-022-04401-w [pii]
AID - 4401 [pii]
AID - 10.1038/s42003-022-04401-w [doi]
PST - epublish
SO  - Commun Biol. 2022 Dec 29;5(1):1421. doi: 10.1038/s42003-022-04401-w.