Asymptomatic Malaria Infection Is Maintained by a Balanced Pro- and Anti-inflammatory Response.
Plasmodium
anti-inflammatory cytokines
asymptomatic malaria
microscopic
pro-inflammatory cytokines
submicroscopic
Journal
Frontiers in microbiology
ISSN: 1664-302X
Titre abrégé: Front Microbiol
Pays: Switzerland
ID NLM: 101548977
Informations de publication
Date de publication:
2020
2020
Historique:
received:
05
05
2020
accepted:
19
10
2020
entrez:
7
12
2020
pubmed:
8
12
2020
medline:
8
12
2020
Statut:
epublish
Résumé
Pro- and anti-inflammatory cytokines are important mediators of immunity and are associated with malaria disease outcomes. However, their role in the establishment of asymptomatic infections, which may precede the development of clinical symptoms, is not as well-understood. We determined the association of pro and anti-inflammatory cytokines and other immune effector molecules with the development of asymptomatic malaria. We measured and compared the plasma levels of pro-inflammatory mediators including tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin (IL)-6, IL-12p70, IL-17A, and granzyme B, the anti-inflammatory cytokine IL-4 and the regulatory cytokine IL-10 from children with asymptomatic malaria infections (either microscopic or submicroscopic) and uninfected controls using Luminex. We show that individuals with microscopic asymptomatic malaria had significantly increased levels of TNF-α and IL-6 compared to uninfected controls. Children with either microscopic or submicroscopic asymptomatic malaria exhibited higher levels of IFN-γ, IL-17A, and IL-4 compared to uninfected controls. The levels of most of the pro and anti-inflammatory cytokines were comparable between children with microscopic and submicroscopic infections. The ratio of IFN-γ/IL-10, TNF-α/IL-10, IL-6/IL-10 as well as IFN-γ/IL-4 and IL-6/IL-4 did not differ significantly between the groups. Additionally, using a principal component analysis, the cytokines measured could not distinguish amongst the three study populations. This may imply that neither microscopic nor submicroscopic asymptomatic infections were polarized toward a pro-inflammatory or anti-inflammatory response. The data show that asymptomatic malaria infections result in increased plasma levels of both pro and anti-inflammatory cytokines relative to uninfected persons. The balance between pro- and anti-inflammatory cytokines are, however, largely maintained and this may in part, explain the lack of clinical symptoms. This is consistent with the generally accepted observation that clinical symptoms develop as a result of immunopathology involving dysregulation of inflammatory mediator balance in favor of pro-inflammatory mediators.
Sections du résumé
BACKGROUND
BACKGROUND
Pro- and anti-inflammatory cytokines are important mediators of immunity and are associated with malaria disease outcomes. However, their role in the establishment of asymptomatic infections, which may precede the development of clinical symptoms, is not as well-understood.
METHODS
METHODS
We determined the association of pro and anti-inflammatory cytokines and other immune effector molecules with the development of asymptomatic malaria. We measured and compared the plasma levels of pro-inflammatory mediators including tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin (IL)-6, IL-12p70, IL-17A, and granzyme B, the anti-inflammatory cytokine IL-4 and the regulatory cytokine IL-10 from children with asymptomatic malaria infections (either microscopic or submicroscopic) and uninfected controls using Luminex.
RESULTS
RESULTS
We show that individuals with microscopic asymptomatic malaria had significantly increased levels of TNF-α and IL-6 compared to uninfected controls. Children with either microscopic or submicroscopic asymptomatic malaria exhibited higher levels of IFN-γ, IL-17A, and IL-4 compared to uninfected controls. The levels of most of the pro and anti-inflammatory cytokines were comparable between children with microscopic and submicroscopic infections. The ratio of IFN-γ/IL-10, TNF-α/IL-10, IL-6/IL-10 as well as IFN-γ/IL-4 and IL-6/IL-4 did not differ significantly between the groups. Additionally, using a principal component analysis, the cytokines measured could not distinguish amongst the three study populations. This may imply that neither microscopic nor submicroscopic asymptomatic infections were polarized toward a pro-inflammatory or anti-inflammatory response.
CONCLUSION
CONCLUSIONS
The data show that asymptomatic malaria infections result in increased plasma levels of both pro and anti-inflammatory cytokines relative to uninfected persons. The balance between pro- and anti-inflammatory cytokines are, however, largely maintained and this may in part, explain the lack of clinical symptoms. This is consistent with the generally accepted observation that clinical symptoms develop as a result of immunopathology involving dysregulation of inflammatory mediator balance in favor of pro-inflammatory mediators.
Identifiants
pubmed: 33281757
doi: 10.3389/fmicb.2020.559255
pmc: PMC7705202
doi:
Types de publication
Journal Article
Langues
eng
Pagination
559255Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2020 Frimpong, Amponsah, Adjokatseh, Agyemang, Bentum-Ennin, Ofori, Kyei-Baafour, Akyea-Mensah, Adu, Mensah, Amoah and Kusi.
Références
Front Immunol. 2019 Oct 15;10:2398
pubmed: 31681289
PLoS One. 2018 Jun 8;13(6):e0198371
pubmed: 29883485
Malar J. 2016 Jul 26;15(1):388
pubmed: 27456336
Front Immunol. 2019 Dec 11;10:2917
pubmed: 31921176
Nature. 2017 Oct 26;550(7677):515-518
pubmed: 29019978
Am J Trop Med Hyg. 2001 Jul;65(1):70-5
pubmed: 11504411
PLoS One. 2018 Jun 15;13(6):e0199172
pubmed: 29906275
Clin Diagn Lab Immunol. 2002 Nov;9(6):1145-52
pubmed: 12414742
Infect Immun. 2004 Oct;72(10):5630-7
pubmed: 15385460
Clin Diagn Lab Immunol. 2002 Mar;9(2):348-51
pubmed: 11874876
BMC Infect Dis. 2018 Aug 29;18(1):432
pubmed: 30157794
Malar J. 2012 Jan 31;11:29
pubmed: 22289302
Vaccine. 2018 Apr 19;36(17):2237-2242
pubmed: 29573877
Nat Rev Immunol. 2019 Jul;19(7):457-471
pubmed: 30940932
Front Immunol. 2019 Feb 12;10:229
pubmed: 30809232
Clin Infect Dis. 2013 Jul;57(1):40-7
pubmed: 23487390
J Infect Dis. 2002 Apr 1;185(7):971-9
pubmed: 11920322
Sci Rep. 2017 Sep 13;7(1):11487
pubmed: 28904345
Infect Dis Obstet Gynecol. 2010;2010:
pubmed: 20706538
J Infect Dis. 2014 Oct 1;210(7):1115-22
pubmed: 24719471
Infect Immun. 2009 Jul;77(7):3033-43
pubmed: 19380468
J Infect Dis. 1999 Jan;179(1):279-82
pubmed: 9841855
Cell Mol Life Sci. 2003 Aug;60(8):1623-35
pubmed: 14504653
Curr Protoc Cytom. 2020 Jun;93(1):e75
pubmed: 32391975
Lancet. 1998 Jun 13;351(9118):1768-72
pubmed: 9635949
Expert Rev Anti Infect Ther. 2013 Jun;11(6):623-39
pubmed: 23750733
PLoS Pathog. 2014 Jan;10(1):e1003864
pubmed: 24415936
Malar J. 2018 Jul 13;17(1):263
pubmed: 30005684
J Allergy Clin Immunol. 2011 Mar;127(3):701-21.e1-70
pubmed: 21377040
Front Immunol. 2017 Oct 19;8:1329
pubmed: 29097996
Am J Trop Med Hyg. 2007 Mar;76(3):470-4
pubmed: 17360869
Parasitol Res. 2018 Sep;117(9):2767-2784
pubmed: 29938323
Am J Clin Exp Immunol. 2017 Feb 15;6(2):9-20
pubmed: 28337387
J Med Entomol. 2005 Sep;42(5):777-9
pubmed: 16363160
Altern Med Rev. 2003 Aug;8(3):223-46
pubmed: 12946237
Biochim Biophys Acta. 2016 Jul;1860(7):1489-97
pubmed: 27080559
Nat Rev Immunol. 2003 Sep;3(9):745-56
pubmed: 12949498
Int Immunol. 2006 Jun;18(6):827-35
pubmed: 16611649
Trends Parasitol. 2004 Dec;20(12):597-603
pubmed: 15522670
Clin Infect Dis. 2008 Dec 1;47(11):1380-7
pubmed: 18947328
Trop Med Int Health. 2004 Aug;9(8):862-8
pubmed: 15303990
Am J Trop Med Hyg. 2007 Dec;77(6 Suppl):88-98
pubmed: 18165479
Acta Trop. 2012 Jul;123(1):53-7
pubmed: 22476130
Nat Immunol. 2008 Jul;9(7):725-32
pubmed: 18563083
Eur Cytokine Netw. 2010 Dec;21(4):232-40
pubmed: 21075740
Parasite Immunol. 2006 Jan-Feb;28(1-2):35-49
pubmed: 16438675
J Clin Lab Immunol. 1991 Mar;34(3):131-9
pubmed: 1667945
Malar J. 2017 Dec 29;16(1):499
pubmed: 29284469
PLoS Pathog. 2015 Jul 16;11(7):e1005041
pubmed: 26182204
J Infect Dis. 2013 May 15;207(10):1590-9
pubmed: 23408847
Sci Rep. 2017 Aug 18;7(1):8844
pubmed: 28821806
Front Immunol. 2019 Jun 18;10:1345
pubmed: 31316497
Clin Vaccine Immunol. 2014 Jun;21(6):859-66
pubmed: 24717969
J Infect Dis. 2006 Jul 15;194(2):198-207
pubmed: 16779726
Trends Parasitol. 2016 Apr;32(4):296-308
pubmed: 26708404
Nat Rev Microbiol. 2014 Dec;12(12):833-40
pubmed: 25329408
Eur J Immunol. 2008 Oct;38(10):2697-705
pubmed: 18825754
Infect Immun. 2005 Jan;73(1):617-21
pubmed: 15618203
Clin Vaccine Immunol. 2017 Apr 5;24(4):
pubmed: 28122790
Immunity. 2006 Aug;25(2):237-47
pubmed: 16901729
Lancet Infect Dis. 2002 Aug;2(8):472-8
pubmed: 12150846