Leishmania donovani infection suppresses Allograft Inflammatory Factor-1 in monocytes and macrophages to inhibit inflammatory responses

Abstract Macrophages and monocytes are important for clearance of Leishmania infections. However, immune evasion tactics employed by the parasite results in suppressed inflammatory responses, marked by deficient macrophage functions and increased accumulation of monocytes. This results in an ineffec...

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Autores principales:	Ricardo Louzada da Silva, Diana M. Elizondo, Nailah Z. D. Brandy, Naomi L. Haddock, Thomas A. Boddie, Laís Lima de Oliveira, Amélia Ribeiro de Jesus, Roque Pacheco de Almeida, Tatiana Rodrigues de Moura, Michael W. Lipscomb
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c64c6eb204154cc6b861c705aa9023ed
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spelling	oai:doaj.org-article:c64c6eb204154cc6b861c705aa9023ed2021-12-02T14:12:09ZLeishmania donovani infection suppresses Allograft Inflammatory Factor-1 in monocytes and macrophages to inhibit inflammatory responses10.1038/s41598-020-79068-62045-2322https://doaj.org/article/c64c6eb204154cc6b861c705aa9023ed2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79068-6https://doaj.org/toc/2045-2322Abstract Macrophages and monocytes are important for clearance of Leishmania infections. However, immune evasion tactics employed by the parasite results in suppressed inflammatory responses, marked by deficient macrophage functions and increased accumulation of monocytes. This results in an ineffective ability to clear parasite loads. Allograft Inflammatory Factor-1 (AIF1) is expressed in myeloid cells and serves to promote immune responses. However, AIF1 involvement in monocyte and macrophage functions during parasitic infections has not been explored. This study now shows that Leishmania donovani inhibits AIF1 expression in macrophages to block pro-inflammatory responses. Mice challenged with the parasite had markedly reduced AIF1 expression in splenic macrophages. Follow-up studies using in vitro approaches confirmed that L. donovani infection in macrophages suppresses AIF1 expression, which correlated with reduction in pro-inflammatory cytokine production and increased parasite load. Ectopic overexpression of AIF1 in macrophages provided protection from infection, marked by robust pro-inflammatory cytokine production and efficient pathogen clearance. Further investigations found that inhibiting AIF1 expression in bone marrow cells or monocytes impaired differentiation into functional macrophages. Collectively, results show that AIF1 is a critical regulatory component governing monocyte and macrophage immune functions and that L. donovani infection can suppress the gene as an immune evasion tactic.Ricardo Louzada da SilvaDiana M. ElizondoNailah Z. D. BrandyNaomi L. HaddockThomas A. BoddieLaís Lima de OliveiraAmélia Ribeiro de JesusRoque Pacheco de AlmeidaTatiana Rodrigues de MouraMichael W. LipscombNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ricardo Louzada da Silva Diana M. Elizondo Nailah Z. D. Brandy Naomi L. Haddock Thomas A. Boddie Laís Lima de Oliveira Amélia Ribeiro de Jesus Roque Pacheco de Almeida Tatiana Rodrigues de Moura Michael W. Lipscomb Leishmania donovani infection suppresses Allograft Inflammatory Factor-1 in monocytes and macrophages to inhibit inflammatory responses
description	Abstract Macrophages and monocytes are important for clearance of Leishmania infections. However, immune evasion tactics employed by the parasite results in suppressed inflammatory responses, marked by deficient macrophage functions and increased accumulation of monocytes. This results in an ineffective ability to clear parasite loads. Allograft Inflammatory Factor-1 (AIF1) is expressed in myeloid cells and serves to promote immune responses. However, AIF1 involvement in monocyte and macrophage functions during parasitic infections has not been explored. This study now shows that Leishmania donovani inhibits AIF1 expression in macrophages to block pro-inflammatory responses. Mice challenged with the parasite had markedly reduced AIF1 expression in splenic macrophages. Follow-up studies using in vitro approaches confirmed that L. donovani infection in macrophages suppresses AIF1 expression, which correlated with reduction in pro-inflammatory cytokine production and increased parasite load. Ectopic overexpression of AIF1 in macrophages provided protection from infection, marked by robust pro-inflammatory cytokine production and efficient pathogen clearance. Further investigations found that inhibiting AIF1 expression in bone marrow cells or monocytes impaired differentiation into functional macrophages. Collectively, results show that AIF1 is a critical regulatory component governing monocyte and macrophage immune functions and that L. donovani infection can suppress the gene as an immune evasion tactic.
format	article
author	Ricardo Louzada da Silva Diana M. Elizondo Nailah Z. D. Brandy Naomi L. Haddock Thomas A. Boddie Laís Lima de Oliveira Amélia Ribeiro de Jesus Roque Pacheco de Almeida Tatiana Rodrigues de Moura Michael W. Lipscomb
author_facet	Ricardo Louzada da Silva Diana M. Elizondo Nailah Z. D. Brandy Naomi L. Haddock Thomas A. Boddie Laís Lima de Oliveira Amélia Ribeiro de Jesus Roque Pacheco de Almeida Tatiana Rodrigues de Moura Michael W. Lipscomb
author_sort	Ricardo Louzada da Silva
title	Leishmania donovani infection suppresses Allograft Inflammatory Factor-1 in monocytes and macrophages to inhibit inflammatory responses
title_short	Leishmania donovani infection suppresses Allograft Inflammatory Factor-1 in monocytes and macrophages to inhibit inflammatory responses
title_full	Leishmania donovani infection suppresses Allograft Inflammatory Factor-1 in monocytes and macrophages to inhibit inflammatory responses
title_fullStr	Leishmania donovani infection suppresses Allograft Inflammatory Factor-1 in monocytes and macrophages to inhibit inflammatory responses
title_full_unstemmed	Leishmania donovani infection suppresses Allograft Inflammatory Factor-1 in monocytes and macrophages to inhibit inflammatory responses
title_sort	leishmania donovani infection suppresses allograft inflammatory factor-1 in monocytes and macrophages to inhibit inflammatory responses
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c64c6eb204154cc6b861c705aa9023ed
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Leishmania donovani infection suppresses Allograft Inflammatory Factor-1 in monocytes and macrophages to inhibit inflammatory responses

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