Role of the aryl hydrocarbon receptor in the immune response profile and development of pathology during Plasmodium berghei Anka infection

Fatima Brant, Aline S. Miranda, Lisia Esper, David Henrique Rodrigues, Lucas Miranda Kangussu, Daniella Bonaventura, Frederico Marianetti Soriani, Vanessa Pinho, Danielle G. Souza, Milene Alvarenga Rachid, Louis M. Weiss, Herbert B. Tanowitz, Mauro Martins Teixeira, Antônio Lucio Teixeira, Fabiana Simão Machado

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Infection with Plasmodium falciparum may result in severe disease affecting various organs, including liver, spleen, and brain, resulting in high morbidity and mortality. Plasmodium berghei Anka infection of mice recapitulates many features of severe human malaria. The aryl hydrocarbon receptor (AhR) is an intracellular receptor activated by ligands important in the modulation of the inflammatory response. We found that AhR-knockout (KO) mice infected with P. berghei Anka displayed increased parasitemia, earlier mortality, enhanced leukocyte-endothelial cell interactions in the brain microvasculature, and increased inflammation in brain (interleukin-17 [IL-17] and IL-6) and liver (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]) compared to infected wild-type (WT) mice. Infected AhR-KO mice also displayed a reduction in cytokines required for host resistance, including TNF-α, IL-1γ, and IFN-β, in the brain and spleen. Infection of AhR-KO mice resulted in an increase in T regulatory cells and transforming growth factor β, IL-6, and IL-17 in the brain. AhR modulated the basal expression of SOCS3 in spleen and brain, and P. berghei Anka infection resulted in enhanced expression of SOCS3 in brain, which was absent in infected AhR-KO mice. These data suggest that AhR-mediated control of SOCS3 expression is probably involved in the phenotype seen in infected AhR-KO mice. This is, to our knowledge, the first demonstration of a role for AhR in the pathogenesis of malaria.

Original languageEnglish (US)
Pages (from-to)3127-3140
Number of pages14
JournalInfection and Immunity
Volume82
Issue number8
DOIs
StatePublished - 2014

Fingerprint

Plasmodium berghei
Aryl Hydrocarbon Receptors
Pathology
Knockout Mice
Infection
Brain
Spleen
Interleukin-17
Malaria
Interleukin-6
Parasitemia
Mortality
Liver
Transforming Growth Factors
Encephalitis
Plasmodium falciparum
Microvessels
Interleukin-1
Cell Communication
Interferon-gamma

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Brant, F., Miranda, A. S., Esper, L., Rodrigues, D. H., Kangussu, L. M., Bonaventura, D., ... Machado, F. S. (2014). Role of the aryl hydrocarbon receptor in the immune response profile and development of pathology during Plasmodium berghei Anka infection. Infection and Immunity, 82(8), 3127-3140. https://doi.org/10.1128/IAI.01733-14

Role of the aryl hydrocarbon receptor in the immune response profile and development of pathology during Plasmodium berghei Anka infection. / Brant, Fatima; Miranda, Aline S.; Esper, Lisia; Rodrigues, David Henrique; Kangussu, Lucas Miranda; Bonaventura, Daniella; Soriani, Frederico Marianetti; Pinho, Vanessa; Souza, Danielle G.; Rachid, Milene Alvarenga; Weiss, Louis M.; Tanowitz, Herbert B.; Teixeira, Mauro Martins; Teixeira, Antônio Lucio; Machado, Fabiana Simão.

In: Infection and Immunity, Vol. 82, No. 8, 2014, p. 3127-3140.

Research output: Contribution to journalArticle

Brant, F, Miranda, AS, Esper, L, Rodrigues, DH, Kangussu, LM, Bonaventura, D, Soriani, FM, Pinho, V, Souza, DG, Rachid, MA, Weiss, LM, Tanowitz, HB, Teixeira, MM, Teixeira, AL & Machado, FS 2014, 'Role of the aryl hydrocarbon receptor in the immune response profile and development of pathology during Plasmodium berghei Anka infection', Infection and Immunity, vol. 82, no. 8, pp. 3127-3140. https://doi.org/10.1128/IAI.01733-14
Brant, Fatima ; Miranda, Aline S. ; Esper, Lisia ; Rodrigues, David Henrique ; Kangussu, Lucas Miranda ; Bonaventura, Daniella ; Soriani, Frederico Marianetti ; Pinho, Vanessa ; Souza, Danielle G. ; Rachid, Milene Alvarenga ; Weiss, Louis M. ; Tanowitz, Herbert B. ; Teixeira, Mauro Martins ; Teixeira, Antônio Lucio ; Machado, Fabiana Simão. / Role of the aryl hydrocarbon receptor in the immune response profile and development of pathology during Plasmodium berghei Anka infection. In: Infection and Immunity. 2014 ; Vol. 82, No. 8. pp. 3127-3140.
@article{c88be276b6274697bb5644189b9cbf31,
title = "Role of the aryl hydrocarbon receptor in the immune response profile and development of pathology during Plasmodium berghei Anka infection",
abstract = "Infection with Plasmodium falciparum may result in severe disease affecting various organs, including liver, spleen, and brain, resulting in high morbidity and mortality. Plasmodium berghei Anka infection of mice recapitulates many features of severe human malaria. The aryl hydrocarbon receptor (AhR) is an intracellular receptor activated by ligands important in the modulation of the inflammatory response. We found that AhR-knockout (KO) mice infected with P. berghei Anka displayed increased parasitemia, earlier mortality, enhanced leukocyte-endothelial cell interactions in the brain microvasculature, and increased inflammation in brain (interleukin-17 [IL-17] and IL-6) and liver (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]) compared to infected wild-type (WT) mice. Infected AhR-KO mice also displayed a reduction in cytokines required for host resistance, including TNF-α, IL-1γ, and IFN-β, in the brain and spleen. Infection of AhR-KO mice resulted in an increase in T regulatory cells and transforming growth factor β, IL-6, and IL-17 in the brain. AhR modulated the basal expression of SOCS3 in spleen and brain, and P. berghei Anka infection resulted in enhanced expression of SOCS3 in brain, which was absent in infected AhR-KO mice. These data suggest that AhR-mediated control of SOCS3 expression is probably involved in the phenotype seen in infected AhR-KO mice. This is, to our knowledge, the first demonstration of a role for AhR in the pathogenesis of malaria.",
author = "Fatima Brant and Miranda, {Aline S.} and Lisia Esper and Rodrigues, {David Henrique} and Kangussu, {Lucas Miranda} and Daniella Bonaventura and Soriani, {Frederico Marianetti} and Vanessa Pinho and Souza, {Danielle G.} and Rachid, {Milene Alvarenga} and Weiss, {Louis M.} and Tanowitz, {Herbert B.} and Teixeira, {Mauro Martins} and Teixeira, {Ant{\^o}nio Lucio} and Machado, {Fabiana Sim{\~a}o}",
year = "2014",
doi = "10.1128/IAI.01733-14",
language = "English (US)",
volume = "82",
pages = "3127--3140",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "8",

}

TY - JOUR

T1 - Role of the aryl hydrocarbon receptor in the immune response profile and development of pathology during Plasmodium berghei Anka infection

AU - Brant, Fatima

AU - Miranda, Aline S.

AU - Esper, Lisia

AU - Rodrigues, David Henrique

AU - Kangussu, Lucas Miranda

AU - Bonaventura, Daniella

AU - Soriani, Frederico Marianetti

AU - Pinho, Vanessa

AU - Souza, Danielle G.

AU - Rachid, Milene Alvarenga

AU - Weiss, Louis M.

AU - Tanowitz, Herbert B.

AU - Teixeira, Mauro Martins

AU - Teixeira, Antônio Lucio

AU - Machado, Fabiana Simão

PY - 2014

Y1 - 2014

N2 - Infection with Plasmodium falciparum may result in severe disease affecting various organs, including liver, spleen, and brain, resulting in high morbidity and mortality. Plasmodium berghei Anka infection of mice recapitulates many features of severe human malaria. The aryl hydrocarbon receptor (AhR) is an intracellular receptor activated by ligands important in the modulation of the inflammatory response. We found that AhR-knockout (KO) mice infected with P. berghei Anka displayed increased parasitemia, earlier mortality, enhanced leukocyte-endothelial cell interactions in the brain microvasculature, and increased inflammation in brain (interleukin-17 [IL-17] and IL-6) and liver (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]) compared to infected wild-type (WT) mice. Infected AhR-KO mice also displayed a reduction in cytokines required for host resistance, including TNF-α, IL-1γ, and IFN-β, in the brain and spleen. Infection of AhR-KO mice resulted in an increase in T regulatory cells and transforming growth factor β, IL-6, and IL-17 in the brain. AhR modulated the basal expression of SOCS3 in spleen and brain, and P. berghei Anka infection resulted in enhanced expression of SOCS3 in brain, which was absent in infected AhR-KO mice. These data suggest that AhR-mediated control of SOCS3 expression is probably involved in the phenotype seen in infected AhR-KO mice. This is, to our knowledge, the first demonstration of a role for AhR in the pathogenesis of malaria.

AB - Infection with Plasmodium falciparum may result in severe disease affecting various organs, including liver, spleen, and brain, resulting in high morbidity and mortality. Plasmodium berghei Anka infection of mice recapitulates many features of severe human malaria. The aryl hydrocarbon receptor (AhR) is an intracellular receptor activated by ligands important in the modulation of the inflammatory response. We found that AhR-knockout (KO) mice infected with P. berghei Anka displayed increased parasitemia, earlier mortality, enhanced leukocyte-endothelial cell interactions in the brain microvasculature, and increased inflammation in brain (interleukin-17 [IL-17] and IL-6) and liver (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]) compared to infected wild-type (WT) mice. Infected AhR-KO mice also displayed a reduction in cytokines required for host resistance, including TNF-α, IL-1γ, and IFN-β, in the brain and spleen. Infection of AhR-KO mice resulted in an increase in T regulatory cells and transforming growth factor β, IL-6, and IL-17 in the brain. AhR modulated the basal expression of SOCS3 in spleen and brain, and P. berghei Anka infection resulted in enhanced expression of SOCS3 in brain, which was absent in infected AhR-KO mice. These data suggest that AhR-mediated control of SOCS3 expression is probably involved in the phenotype seen in infected AhR-KO mice. This is, to our knowledge, the first demonstration of a role for AhR in the pathogenesis of malaria.

UR - http://www.scopus.com/inward/record.url?scp=84904726496&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904726496&partnerID=8YFLogxK

U2 - 10.1128/IAI.01733-14

DO - 10.1128/IAI.01733-14

M3 - Article

C2 - 24818665

AN - SCOPUS:84904726496

VL - 82

SP - 3127

EP - 3140

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 8

ER -