CoChat
Sign Up
Cited by 193Immune Response and InflammationMalaria Research and ControlInflammasome and immune disorders

Malaria primes the innate immune response due to interferon-γ induced enhancement of toll-like receptor expression and function

Open access
Franklin, Bernardo S., Parroche, Peggy, Ataíde, Marco Antǒnio, Lauw, Fanny, Ropert, Catherine, de Oliveira, Rosane B., Pereira, Dhelio, Tada, Mauro Shugiro +5 more·2009·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0809742106PMC PMC2657593
Open this paper in CoChat — free account

Abstract

Malaria-induced sepsis is associated with an intense proinflammatory cytokinemia for which the underlying mechanisms are poorly understood. It has been demonstrated that experimental infection of humans with Plasmodium falciparum primes Toll-like receptor (TLR)-mediated proinflammatory responses. Nevertheless, the relevance of this phenomenon during natural infection and, more importantly, the mechanisms by which malaria mediates TLR hyperresponsiveness are unclear. Here we show that TLR responses are boosted in febrile patients during natural infection with P. falciparum . Microarray analyses demonstrated that an extraordinary percentage of the up-regulated genes, including genes involving TLR signaling, had sites for IFN-inducible transcription factors. To further define the mechanism involved in malaria-mediated “priming,” we infected mice with Plasmodium chabaudi . The human data were remarkably predictive of what we observed in the rodent malaria model. Malaria-induced priming of TLR responses correlated with increased expression of TLR mRNA in a TLR9-, MyD88-, and IFNγ-dependent manner. Acutely infected WT mice were highly susceptible to LPS-induced lethality while TLR9 −/− , IL12 −/− and to a greater extent, IFNγ −/− mice were protected. Our data provide unprecedented evidence that TLR9 and MyD88 are essential to initiate IL12 and IFNγ responses and favor host hyperresponsiveness to TLR agonists resulting in overproduction of proinflammatory cytokines and the sepsis-like symptoms of acute malaria.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1073/pnas.0809742106

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The phenomenon of enhanced TLR responsiveness was also observed in mice infected with Plasmodium chabaudi in a TLR9/IL-12/IFN-gamma-dependent manner.

    “This phenomenon was also observed, in a TLR9/IL-12/IFN-␥-dependent manner, in mice infected with Plasmodium chabaudi (50).”

    From Into the Eye of the Cytokine Storm (2012) · cites this paper as [50]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

1 retracted

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Franklin, B. S., Parroche, P., Ataíde, M. A., Lauw, F., Ropert, C., de Oliveira, R. B., Pereira, D., Tada, M. S., Nogueira, P., da Silva, L. H. P., Bjorkbacka, H., Golenbock, D. T., & Gazzinelli, R. T.
Affiliations
  • University of Massachusetts Chan Medical School (US)
  • Immunopathology Laboratory, René Rachou Institute, Fundaçao Oswaldo Cruz, Avenue Augusto de Lima 1715, MG 30190, Belo Horizonte, Brazil;
  • Fiocruz Minas (BR)
  • Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605;
  • Centro de Pesquisas em Medicina Tropical de Rondônia, 364, Km 4.5, RO 78900, Porto Velho, Brazil;
  • Experimental Cardiovascular Research, Lund University, SE-205 02 Malmö, Sweden; and
  • Universidade Federal de Minas Gerais (BR)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2009-04-07
Volume
106
Issue
14
Pages
5789-5794
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0809742106
PMC
PMC2657593
OpenAlex
W1991773233
Cited by
193
References
44
Citations by year
2026: 6 · 2025: 4 · 2024: 3 · 2023: 8 · 2022: 6 · 2021: 7 · 2020: 15 · 2019: 14 · 2018: 12 · 2017: 6 · 2016: 10 · 2015: 8 · 2014: 16 · 2013: 17 · 2012: 27
FWCI
8.77
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion, other-oa)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
  • Americanae (AECID Library) (submittedVersion, other-oa)
  • Arca - Repositório Institucional da Fiocruz (submittedVersion, other-oa)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • National Institute of Allergy and Infectious Diseases (R21AI060737)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords
malaria, Plasmodium falciparum, Plasmodium chabaudi, innate immune priming, TLR9, MyD88, interferon-gamma, IL-12, Toll-like receptor signaling, sepsis, inflammatory cytokines, TLR9 knockout mice, febrile malaria
MeSH terms
Animals, Fever, Humans, Immunity, Innate, Inflammation, Interferon-gamma, Malaria, Plasmodium falciparum, Transcription Factors, Up-Regulation, Cytokines, Plasmodium chabaudi, Interleukin-12, Sepsis, Gene Expression Profiling, Toll-Like Receptors, Toll-Like Receptor 9, Mice, Myeloid Differentiation Factor 88

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review