Endodontic Infection–induced Inflammation Resembling Osteomyelitis of the Jaws in Toll-like Receptor 2/Interleukin 10 Double-knockout Mice

ABSTRACT Infection of interleukin-10 (IL-10)-nonexpressing (IL-10−/−) mice with Plasmodium chabaudi chabaudi (AS) leads to exacerbated pathology in female mice and death in a proportion of them. Hypoglycemia, hypothermia, and loss in body weight were significantly greater in female IL-10−/−mice than in male knockout mice and all wild-type (WT) mice during the acute phase of infection. At this time, both female and male IL-10−/− mice produced more gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and IL-12p40 mRNA than their respective WT counterparts. Inactivation of IFN-γ in IL-10−/− mice by the injection of anti-IFN-γ antibodies or by the generation of IL-10−/− IFN-γ receptor−/− double-knockout mice resulted in reduced mortality but did not affect body weight, temperature, or blood glucose levels. The data suggest that IFN-γ-independent pathways may be responsible for these pathological features of P. chabaudimalaria and may be due to direct stimulation of TNF-α by the parasite. Since male and female knockout mice both produce more inflammatory cytokines than their WT counterparts, it is likely that the mortality seen in females is due to the nature or magnitude of the response to these cytokines rather than the amount of IFN-γ or TNF-α produced.

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Regulatory Actions of Toll-Like Receptor 2 (TLR2) and TLR4 in Leishmania donovani Infection in the Liver

Infection and Immunity ◽

10.1128/iai.01468-12 ◽

2013 ◽

Vol 81 (7) ◽

pp. 2318-2326 ◽

Cited By ~ 24

Author(s):

Henry W. Murray ◽

Yunhua Zhang ◽

Yan Zhang ◽

Vanitha S. Raman ◽

Steven G. Reed ◽

...

Keyword(s):

Mrna Expression ◽

Leishmania Donovani ◽

Interleukin 10 ◽

Inos Mrna ◽

Toll Like Receptor ◽

Content Type ◽

Toll Like Receptor 2 ◽

Ifn Γ ◽

Low Dose Chemotherapy ◽

Oxide Synthase

ABSTRACTIn livers of susceptible but self-curing C57BL/6 mice, intracellularLeishmania donovaniinfection enhanced Toll-like receptor 4 (TLR4) and TLR2 gene expression. In the liver, infected TLR4−/−mice showed reduced gamma interferon (IFN-γ), tumor necrosis factor (TNF), and inducible nitric oxide synthase (iNOS) mRNA expression, higher-level and slowly resolving infection, delayed granuloma formation, and little response to low-dose chemotherapy; in serum, the ratio of IFN-γ to interleukin 10 (IL-10) activity was decreased by 50%. In contrast, in TLR2−/−mice, control of liver infection, parasite killing, and granuloma assembly were accelerated and chemotherapy's efficacy enhanced. In livers of infected TLR2−/−mice, mRNA expression was not increased for inflammatory cytokines or iNOS or decreased for IL-10; however, the serum IFN-γ/IL-10 ratio was increased 6.5-fold and minimal responses to IL-10 receptor blockade suggested downregulated IL-10. In established infection in wild-type mice, blockading TLR2 induced parasite killing and triggering TLR4 strengthened resistance and promoted chemotherapy's effect. Thus, in experimentalL. donovaniinfection in the liver, TLR4 signaling upregulates and TLR2 signaling downregulates macrophage antileishmanial activity, making both receptors potential therapeutic targets in visceral leishmaniasis for engagement (TLR4) or blockade (TLR2).

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Toll-Like Receptor 2 Agonist Pam3CSK4 Alleviates the Pathology of Leptospirosis in Hamster

Infection and Immunity ◽

10.1128/iai.00708-16 ◽

2016 ◽

Vol 84 (12) ◽

pp. 3350-3357 ◽

Cited By ~ 13

Author(s):

Wenlong Zhang ◽

Naisheng Zhang ◽

Xufeng Xie ◽

Jian Guo ◽

Xuemin Jin ◽

...

Keyword(s):

Tissue Injury ◽

Interleukin 10 ◽

Peritoneal Macrophages ◽

High Ratio ◽

Toll Like Receptor ◽

Wild Type ◽

Necrosis Factor Alpha ◽

Content Type ◽

Target Organs ◽

Toll Like Receptor 2

Leptospirosis, caused by pathogenic spirochetes, is a zoonotic disease of global importance. The detailed pathogenesis of leptospirosis is still unclear, which limits the ideal treatment of leptospirosis. In this study, we analyzed the expression of Toll-like receptor 2 (TLR2) and TLR4 in target organs of both resistant mice and susceptible hamsters after Leptospira interrogans serovar Autumnalis infection. TLR2 but not TLR4 transcripts in mouse organs contrasted with delayed induction and overexpression in hamster organs. Coinjection of leptospires and the TLR2 agonist Pam3CSK4 into hamsters improved their survival rate, alleviated tissue injury, and decreased the abundance of leptospires in target organs. The production of interleukin-10 (IL-10) from tissues was enhanced in hamsters of the group coinjected with leptospires and Pam3CSK4 compared with the leptospira-injected group. Similarly, IL-10 levels in TLR2-deficient mice were lower than those in wild-type mice. A high ratio of IL-10/tumor necrosis factor alpha (TNF-α) levels was found in both infected wild-type mice and hamsters coinjected with leptospires and Pam3CSK4. Moreover, TLR2-dependent IL-10 expression was detected in peritoneal macrophages after leptospira infection. Our data demonstrate that coinjection of leptospires and Pam3CSK4 alleviates the pathology of leptospirosis in hamsters; this effect may result from the enhanced expression of TLR2-dependent IL-10.

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Toll-like receptor-2 (TLR2); Toll-like receptor-4 (TLR4); interleukin-10 (IL-10)

Science-Business eXchange ◽

10.1038/scibx.2008.41 ◽

2008 ◽

Vol 1 (2) ◽

pp. 41-41 ◽

Cited By ~ 1

Keyword(s):

Interleukin 10 ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Toll Like Receptor 2

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Decreased inflammatory response in Toll-like receptor 2 knockout mice is associated with exacerbated Pneumocystis pneumonia

Microbes and Infection ◽

10.1016/j.micinf.2007.12.014 ◽

2008 ◽

Vol 10 (4) ◽

pp. 334-341 ◽

Cited By ~ 16

Author(s):

Shao-Hung Wang ◽

Chen Zhang ◽

Mark E. Lasbury ◽

Chung-Ping Liao ◽

Pamela J. Durant ◽

...

Keyword(s):

Inflammatory Response ◽

Knockout Mice ◽

Pneumocystis Pneumonia ◽

Toll Like Receptor ◽

Toll Like Receptor 2

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Expression of toll-like receptor 2 and plasma level of interleukin-10 are associated with outcome in tuberculosis

European Journal of Clinical Microbiology & Infectious Diseases ◽

10.1007/s10096-012-1572-3 ◽

2012 ◽

Vol 31 (9) ◽

pp. 2327-2333 ◽

Cited By ~ 9

Author(s):

J.-Y. Wang ◽

H.-C. Chang ◽

J.-L. Liu ◽

C.-C. Shu ◽

C.-H. Lee ◽

...

Keyword(s):

Plasma Level ◽

Interleukin 10 ◽

Toll Like Receptor ◽

Toll Like Receptor 2

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Lipopolysaccharidefrom the Periodontal Pathogen Porphyromonas gingivalisPrevents Apoptosis of HL60-Derived Neutrophils InVitro

Infection and Immunity ◽

10.1128/iai.71.12.7232-7235.2003 ◽

2003 ◽

Vol 71 (12) ◽

pp. 7232-7235 ◽

Cited By ~ 37

Author(s):

D. A Murray ◽

J. M. A. Wilton

Keyword(s):

Porphyromonas Gingivalis ◽

Interleukin 10 ◽

Periodontal Pathogen ◽

Toll Like Receptor ◽

Inhibiting Effect ◽

Periodontal Inflammation ◽

Toll Like Receptor 2

ABSTRACT Lipopolysaccharide (LPS) from Porphyromonas gingivalis prevented apoptosis of HL60-derived neutrophils, which could not be restored upon the addition of interleukin-10. Signaling of P. gingivalis LPS through Toll-like receptor 2 (TLR2), not TLR4, may account for the inhibiting effect of P. gingivalis LPS on apoptosis and provide a mechanism for the development of destructive periodontal inflammation.

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Yersinia V–Antigen Exploits Toll-like Receptor 2 and CD14 for Interleukin 10–mediated Immunosuppression

Journal of Experimental Medicine ◽

10.1084/jem.20020908 ◽

2002 ◽

Vol 196 (8) ◽

pp. 1017-1024 ◽

Cited By ~ 249

Author(s):

Andreas Sing ◽

Dagmar Rost ◽

Natalia Tvardovskaia ◽

Andreas Roggenkamp ◽

Agnès Wiedemann ◽

...

Keyword(s):

Immune Response ◽

Defense Mechanisms ◽

Cell Activation ◽

Yersinia Pseudotuberculosis ◽

Interleukin 10 ◽

Toll Like Receptor ◽

Toll Like Receptor 2 ◽

V Antigen ◽

Enteropathogenic Yersinia ◽

The Impact

A characteristic of the three human-pathogenic Yersinia spp. (the plague agent Yersinia pestis and the enteropathogenic Yersinia pseudotuberculosis and Yersinia enterocolitica) is the expression of the virulence (V)-antigen (LcrV). LcrV is a released protein which is involved in contact-induced secretion of yersinia antihost proteins and in evasion of the host's innate immune response. Here we report that recombinant LcrV signals in a CD14- and toll-like receptor 2 (TLR2)-dependent fashion leading to immunosuppression by interleukin 10 induction. The impact of this immunosuppressive effect for yersinia pathogenesis is underlined by the observation that TLR2-deficient mice are less susceptible to oral Y. enterocolitica infection than isogenic wild-type animals. In summary, these data demonstrate a new ligand specificity of TLR2, as LcrV is the first known secreted and nonlipidated virulence-associated protein of a Gram-negative bacterium using TLR2 for cell activation. We conclude that yersiniae might exploit host innate pattern recognition molecules and defense mechanisms to evade the host immune response.

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