CoChat
Sign Up
Cited by 269Immune Response and InflammationSepsis Diagnosis and TreatmentInflammation biomarkers and pathways

Resilience to Bacterial Infection: Difference between Species Could Be Due to Proteins in Serum

Open access
Warren, H. Shaw, Fitting, Catherine, Hoff, Eva, Adib‐Conquy, Minou, Beasley‐Topliffe, Laura, Tesini, Brenda, Liang, Xueya, Valentine, Catherine +3 more·2010·The Journal of Infectious Diseases
DOI 10.1086/649557PMC PMC2798011
Open this paper in CoChat — free account

Abstract

Vertebrates vary in resistance and resilience to infectious diseases, and the mechanisms that regulate the trade-off between these often opposing protective processes are not well understood. Variability in the sensitivity of species to the induction of damaging inflammation in response to equivalent pathogen loads (resilience) complicates the use of animal models that reflect human disease. We found that induction of proinflammatory cytokines from macrophages in response to inflammatory stimuli in vitro is regulated by proteins in the sera of species in inverse proportion to their in vivo resilience to lethal doses of bacterial lipopolysaccharide over a range of 10,000-fold. This finding suggests that proteins in serum rather than intrinsic cellular differences may play a role in regulating variations in resilience to microbe-associated molecular patterns between species. The involvement of circulating proteins as key molecules raises hope that the process might be manipulated to create better animal models and potentially new drug targets.

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 · 10.1086/649557

Cites

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?

  • TLR4 on murine KCs is less responsive, meaning that mice exhibit a weaker response to bacteria and bacterial products.

    “Treg, while TLR4 on murine KCs is less responsive meaning that mice exhibit a weaker response to bacteria and bacterial products(53).”

    From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [53]

    The Results (whole-blood comparison; page not provided) show that mouse blood produced much less TNF and IL-6 than human blood after exposure to bacterial products or heat-killed bacteria. But the Introduction says isolated mouse macrophages respond to TLR agonists at roughly similar concentrations to human cells, and the paper does not establish that TLR4 on murine Kupffer cells (KCs) is intrinsically less responsive. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • TLR2 and TLR9 participate in alcohol-mediated liver injury by inducing CXCL1 expression and neutrophil infiltration.

    “TLR2 and TLR9 participate in alcohol-mediated liver injury by inducing CXCL1 expression and neutrophil infiltration (53).”

    From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [53]

    The Results section discusses TLR2 agonists and TNF production in monocytes, while the Discussion addresses responses to bacterial infection. A search for alcohol-mediated liver injury, CXCL1, TLR9, and neutrophil infiltration found no passage addressing the claimed mechanism; no page numbers were available in our copy. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

Self-check

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

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

The citation lists haven’t been fetched yet

References 35 · Cited by 269

Research works printed but not linked: 36

  1. [1]Schneider DS Ayres JS Two ways to survive infection: what resistance and tolerance can teach us about treating infectious diseases Nat Rev Immunol 2008 8 11 889 895 18927577 PMC4368196
  2. [2]Raberg L Sim D Read AF Disentangling genetic variation for resistance and tolerance to infectious diseases in animals Science 2007 318 5851 812 814 17975068
  3. [3]Glode LM Mergenhagen SE Rosenstreich DL Significant contribution of spleen cells in mediating the lethal effects of endotoxin in vivo Infect Immun 1976 14 3 626 630 965087 PMC420932
  4. [4]McCuskey RS McCuskey PA Urbaschek R Urbaschek B Species differences in Kupffer cells and endotoxin sensitivity Infect Immun 1984 45 1 278 280 6376358 PMC263314
  5. [5]Schaedler R Dubos RJ The susceptibility of mice to bacterial endotoxins J Exp Med 1961 113 559 570 13747161 PMC2137366
  6. [6]Reynolds K Novosad B Hoffhines A Gipson J Johnson J Peters J Pretreatment with troglitazone decreases lethality during endotoxemia in mice J Endotoxin Res 2002 8 4 307 314 12230920
  7. [7]van der Poll T Lowry SF Tellado JM Forse RA Solomkin Basel JS Biological responses to endotoxin in humans Modulation of the Inflammatory Responsein Severe Sepsis 1995 Switzerland Karger 18 32 1995; 20: 18–32
  8. [9]Sauter C Wolfensberger C Interferon in human serum after injection of endotoxin Lancet 1980 2 8199 852 853 6159510
  9. [10]Liu CT Sanders RP Modification of lethality induced by staphylococcal enterotoxin B in Dutch rabbits Am J Vet Res 1980 41 3 399 404 7369614
  10. [11]Chen JY Qiao Y Komisar JL Baze WB Hsu IC Tseng J Increased susceptibility to staphylococcal enterotoxin B intoxication in mice primed with actinomycin D Infect Immun 1994 62 10 4626 4631 7927730 PMC303153
  11. [12]Mathison JC Wolfson E Ulevitch RJ Participation of tumor necrosis factor in the mediation of gram negative bacterial lipopolysaccharide-induced injury in rabbits J Clin Invest 1988 81 1925 1937 3384955 PMC442645
  12. [14]Beutler B Milsark IW Cerami AC Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin Science 1985 229 869 871 3895437
  13. [15]Freudenberg MA Keppler D Galanos C Requirement for lipopolysaccharide-responsive macrophages in galactosamine-induced sensitization to endotoxin Infect Immun 1986 51 3 891 895 3949385 PMC260982
  14. [16]Michalek SM Moore RN McGhee JR Rosenstreich DL Mergenhagen SE The primary role of lymphoreticular cells in the mediation of host responses to bacterial endotoxim J Infect Dis 1980 141 1 55 63 6154108
  15. [17]Hellman J Roberts JDJ Tehan MM Allaire JE Warren HS Bacterial peptidoglycan-associated lipoprotein is released into the bloodstream in gram-negative sepsis and causes inflammation and death in mice J Biol Chem 2002 277 16 14274 14280 11830585
  16. [18]Warren HS Amato SF Fitting C Black KM Loiselle PM Pasternack MS Assessment of ability of murine and human anti-lipid A monoclonal antibodies to bind and neutralize lipopolysaccharide J Exp Med 1993 177 89 97 8418211 PMC2190862
  17. [19]Bagchi A Herrup EA Warren HS Trigilio J Shin HS Valentine C MyD88-Dependent and MyD88-Independent Pathways in Synergy, Priming, and Tolerance between TLR Agonists J Immunol 2007 178 2 1164 1171 17202381
  18. [20]Marie C Pitton C Fitting C Cavaillon JM IL-10 and IL-4 synergize with TNF-alpha to induce IL-1ra production by human neutrophils Cytokine 1996 8 2 147 151 8777273
  19. [21]Wilson BMG Severn A Rapson NT Chana J Hopkins P A convenient human whole blood culture system for studying the regulation of tumour necrosis factor release by bacterial lipopolysaccharide J Immunol Methods 1991 139 233 240 1904465
  20. [22]Adib-Conquy M Adrie C Moine P Asehnoune K Fitting C Pinsky MR NF-κB expression in mononuclear cells of septic patients resembles that observed in LPS-tolerance Am J Respir Crit Care Med 2000 162 1877 1883 11069829
  21. [23]Adib-Conquy M Moine P Asehnoune K Edouard A Espevik T Miyake K Toll-like receptors-mediated TNF and IL-10 production differ during systemic inflammation Am J Respir Crit Care Med 2003 168 2 158 164 12738604
  22. [24]Adib-Conquy M Adrie C Fitting C Gattolliat O Beyaert R Cavaillon JM Up-regulation of MyD88s and SIGIRR, molecules inhibiting Toll-like receptor signaling, in monocytes from septic patients Crit Care Med 2006 34 9 2377 2385 16850005
  23. [25]Sheagren JN Wolff SM Shulman NR Febrile and hematologic responses of rhesus monkeys to bacterial endotoxin Am J Physiol 1967 212 4 884 890 4960791
  24. [26]Golenbock DT Will JA Raetz CR Proctor RA Lipid X ameliorates pulmonary hypertension and protects sheep from death due to endotoxin Infect Immun 1987 55 10 2471 2476 3308707 PMC260732
  25. [27]Schiffer ER Reber G De Moerloose P Morel DR Evaluation of unfractionated heparin and recombinant hirudin on survival in a sustained ovine endotoxin shock model Crit Care Med 2002 30 12 2689 2699 12483060
  26. [28]Ohtsuka H Higuchi T Matsuzawa H Sato H Takahashi K Takahashi J Inhibitory effect on LPS-induced tumor necrosis factor in calves treated with chlorpromazine or pentoxifylline J Vet Med Sci 1997 59 11 1075 1077 9409530
  27. [29]Clark IA Correlation between susceptibility to malaria and babesia parasites and to endotoxicity Trans R Soc Trop Med Hyg 1982 76 1 4 7 7043806
  28. [30]Goldfarb RD Tambolini W Wiener SM Weber PB Canine left ventricular performance during LD50 endotoxemia Am J Physiol 1983 244 3 H370 H377 6338743
  29. [31]Cobb JP Natanson C Quezado ZM Hoffman WD Koev CA Banks S Differential hemodynamic effects of L-NMMA in endotoxemic and normal dogs Am J Physiol 1995 268 4 Pt 2 H1634 H1642 7733365
  30. [32]Adler HE DaMassa AJ Toxicity of endotoxin to chicks Avian Dis 1979 23 1 174 178 486001
  31. [33]Berczi I Bertok L Bereznai T Comparative studies on the toxicity of Escherichia coli lipopolysaccharide endotoxin in various animal species Can J Microbiol 1966 12 5 1070 1071 5339644
  32. [34]Hansen MB Nielsen SE Berg K Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill J Immunol Methods 1989 119 2 203 210 2470825
  33. [35]Cavaillon JM Adib-Conquy M Bench-to-bedside review: endotoxin tolerance as a model of leukocyte reprogramming in sepsis Crit Care 2006 10 5 233 17044947 PMC1751079
  34. [36]O'Brien AD Rosenstreich DL Scher I Campbell GH MacDermott RP Formal SB Genetic control of susceptibility to Salmonella typhimurium in mice: role of the LPS gene J Immunol 1980 124 1 20 24 6985638
  35. [37]Montminy SW Khan N McGrath S Walkowicz MJ Sharp F Conlon JE Virulence factors of Yersinia pestis are overcome by a strong lipopolysaccharide response Nat Immunol 2006 7 10 1066 1073 16980981
  36. [38]Munford RS Detoxifying endotoxin: time, place and person J Endotoxin Res 2005 11 2 69 84 15949133

Authors
Warren, H. S., Fitting, C., Hoff, E., Adib‐Conquy, M., Beasley‐Topliffe, L., Tesini, B., Liang, X., Valentine, C., Hellman, J., Hayden, D., & Cavaillon, J.
Affiliations
  • Institut Pasteur (FR)
  • Massachusetts General Hospital (US)
Corresponding author
Warren, H. Shaw
ORCID
Venue
The Journal of Infectious Diseases
Publisher
Oxford University Press (OUP)
Published
2010-01-15
Volume
201
Issue
2
Pages
223-232
ISSN
  • 0022-1899 (ISSN-L)
  • 1537-6613
DOI
10.1086/649557
PMC
PMC2798011
OpenAlex
W2162114403
Cited by
269
References
35
Citations by year
2026: 10 · 2025: 13 · 2024: 20 · 2023: 12 · 2022: 16 · 2021: 20 · 2020: 20 · 2019: 26 · 2018: 23 · 2017: 17 · 2016: 16 · 2015: 13 · 2014: 21 · 2013: 14 · 2012: 16
FWCI
4.03
Type
journal article
Language
en
Open access
Locations
  • The Journal of Infectious Diseases (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of General Medical Sciences (R01GM059694, GM 59694)
  • National Institute of Allergy and Infectious Diseases (AI059010, R01AI059010, T32AI007061)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Keywords
bacterial lipopolysaccharide, serum proteins, inflammatory cytokines, macrophages, inflammation, interspecies variation, microbe-associated molecular patterns, animal models of infection, host defense
MeSH terms
Animals, Bacterial Outer Membrane Proteins, Cardenolides, Cells, Cultured, Disease Models, Animal, Humans, Immunity, Innate, Lipoproteins, Macrophage Activation, Macrophages, Peptidoglycan, Saponins, Species Specificity, Bacteremia, Escherichia coli Proteins, Mice

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