Caspase-1 Activation of IL-1β and IL-18 Are Essential for Shigella flexneri–Induced Inflammation

Sansonetti, Philippe J.; Phalipon, Armelle; Arondel, Josette; Thirumalai, Kavitha; Banerjee, Subhashis; Akira, Shizuo; Takeda, Kiyoshi; Zychlinsky, Arturo

doi:10.1016/s1074-7613(00)80209-5

Cited by 368 publications

(299 citation statements)

References 42 publications

Supporting

Mentioning

286

Contrasting

Unclassified

Order By: Relevance

“…This cannot be ascribed to a defect in the ability of the recombinant bacteria to enter epithelial cells or to spread between cells, because recombinant strains were shown to be able to invade and spread between cells as efficiently as the wild type in vitro. The data obtained with IL-1ra-secreting Shigella are in line with a previous work (38) showing that in contrast to wild-type mice, the i.n. inoculation of IL-1␤-deficient mice with M90T strain resulted in the localization of bacteria at restricted infectious foci within lung tissues.…”

Section: Discussionsupporting

confidence: 91%

“…H&E staining was done as previously described (36). Inflammation index, representing the percentage of inflammatory area recorded in a series of sections covering the whole lung, was calculated as previously described (38). LPS immunostaining was realized with an anti-S. flexneri 5a LPS Ab (IgGC20) conjugated to alcaline phosphatase (39).…”

Section: Histopathological Analysismentioning

confidence: 99%

See 1 more Smart Citation

Delivery of Biologically Active Anti-Inflammatory Cytokines IL-10 and IL-1ra In Vivo by the Shigella Type III Secretion Apparatus

Chamekh

Phalipon

Quertainmont

et al. 2008

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Pathogenicity of many Gram-negative bacteria relies on a type III secretion (T3S) apparatus, which is used for delivery of bacterial effectors into the host cell cytoplasm allowing the bacteria to manipulate host cell cytoskeleton network as well as to interfere with intracellular signaling pathways. In this study, we investigated the potential of the Shigella flexneri T3SA as an in vivo delivery system for biologically active molecules such as cytokines. The anti-inflammatory cytokines IL-10 and IL-1 receptor antagonist (IL-1ra) were genetically fused to the first 30 or 60 residues of the Shigella T3S effector IpaH9.8 or to the first 50 residues of the Yersinia enterocolitica effector YopE and the recombinant fusion proteins were expressed in S. flexneri. YopE50-IL-10, IpaH60-IL-10, and IpaH60-IL-1ra were efficiently secreted via the T3S apparatus of Shigella. Moreover, these recombinant proteins did not impair the invasive ability of the bacteria in vitro. In a murine model, Shigella strains expressing YopE50-IL-10, IpaH60-IL-10, and IpaH60-IL-1ra induced a lower mortality in mice that was associated with reduced inflammation and a restricted localization of bacteria within the lung tissues as compared with wild-type Shigella. Moreover, the level of TNF-α and IL-1β mRNA were reduced in the lungs following infection by IL-10- and IL-1ra-secreting Shigella, respectively. These findings demonstrate that the Shigella T3S apparatus can deliver biologically active cytokines in vivo, thus opening new avenues for the use of attenuated bacteria to deliver proteins for immunomodulation or gene therapy purposes.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Histopathological Analysismentioning

confidence: 99%

Delivery of Biologically Active Anti-Inflammatory Cytokines IL-10 and IL-1ra In Vivo by the Shigella Type III Secretion Apparatus

Chamekh

Phalipon

Quertainmont

et al. 2008

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The ABHD-enhancing effect of IL-18 at 10 ng, but not at higher or lower doses, suggests its importance in the differential enhancement of ABHD by LPS. This may further be supported by the previously reported association of high IL-18 levels with 1) IFN-␥-mediated lethal liver injury induced in heat-killed Propionibacterium acnes-challenged cas-1 transgenic mice (43); 2) LPS-induced lethality in P. acnes-primed mice (35, 44); 3) lethal endotoxemia (11,28); and 4) the excessive inflammation observed during acute experimental shigellosis (45). However, our studies do not rule out other mechanism(s) involved in LPS-induced ABHD.…”

Section: Discussionsupporting

confidence: 60%

IL-18 Levels and the Outcome of Innate Immune Response to Lipopolysaccharide: Importance of a Positive Feedback Loop with Caspase-1 in IL-18 Expression

Joshi

Kalvakolanu

Hasday

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

LPS enhanced antibacterial host defenses (ABHD) when given at low (75 μg) doses (16 of 19 mice survived 3× LD50 Escherichia coli vs 3 of 19 LPS-naive mice; p = 0.0001), but induced lethal inflammation at high (500 μg) doses (5 of 5 died). Differences in the cytokine profiles induced by these LPS doses may provide insight into the mechanism(s) of transition from beneficial to lethal LPS responses. The 75 μg LPS induced 5.9 ± 0.9 ng/ml serum IL-18 at 8 h, which decreased to 2.3 ± 0.4 ng/ml by 24 h, whereas 500 μg LPS induced 11.1 ± 1.6 ng/ml serum IL-18 levels at 8 h, which increased until death. Compared with 75 μg, higher but sublethal (150 μg) doses of LPS induced greater serum IL-18 levels and less effectively induced ABHD (3 of 8 survived). Reduction of serum IL-18 with neutralizing Ab improved the ABHD induced by 150 μg, but reduced that produced by 75 μg LPS, suggesting an optimal range of serum IL-18 level was essential for efficient ABHD. Increased expression of caspase-1 mRNA in response to the higher IL-18 levels induced at the 150 and 500 μg, but not at the 75 μg doses of LPS may represent a positive feedback regulatory loop leading to sustained serum IL-18 levels. We conclude that the regulation of serum IL-18 expression is critical to the outcome of innate immune responses to LPS.

show abstract

“…Detection of the PAMP or danger signals in the inflammasome is achieved by proteins of the NOD-like receptor family such as NALP3, NALP1 or IPAF, leading to a conformational change and caspase-1 activation [14]. Caspase-1 activity is essential in host defenses against infection with Francisella tularensis [15], Legionella pneumophila [16], Shigella [17] and Pseudomonas aeruginosa [18]. The fact that IL-1b and IFN-g play an important role during infection with M. tuberculosis and are regulated by caspase-1 activity suggests that inflammasome activation may be important for anti-mycobacterial defense mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional and inflammasome‐mediated pathways for the induction of IL‐1β production by Mycobacterium tuberculosis

et al. 2009

View full text Add to dashboard Cite

Proinflammatory cytokines of the IL-1 family play an important role for the anti-mycobacterial host defense mechanisms. In the present study we have deciphered the pathways leading from recognition of Mycobacterium tuberculosis to the production and release of IL-1b, the most important member of the IL-1 family. By stimulating cells defective in various pattern recognition receptors, we could demonstrate that IL-1b production is induced by M. tuberculosis through pathways involving TLR2/TLR6 and NOD2 receptors. In contrast, TLR4, TLR9 and TLR1 receptors are not involved in IL-1b induction. Recognition of M. tuberculosis by TLR and NOD2 leads to transcription of proIL-1b through mechanisms involving ERK, p38 and Rip2, but not JNK. Interestingly, although caspase-1 is necessary for the processing of proIL-1b, activation of caspase-1 is not dependent on the stimulation of cells by M. tuberculosis. Monocytes expressed constitutively active caspase-1. The secretion of IL-1b is dependent on the activation of P2X7-induced pathways by endogenously released ATP. In conclusion, we have dissected the molecular mechanisms responsible for IL-1b production by M. tuberculosis, and that may contribute to a deeper knowledge of the mechanisms of cell activation by M. tuberculosis.Key words: Cytokines . Infections -bacterial . Inflammation IntroductionIt is estimated that approximately one-third of the world population is infected with Mycobacterium tuberculosis, the agent causing tuberculosis (TB), although only 5% of these individuals will eventually develop clinical disease. The WHO estimated that 1.6 million deaths resulted from TB in 2005, equaling 4400 deaths a day [1]. The highest rates of infection and especially the mortality are seen in the developing countries, and rates continue to climb in countries where the prevalence of HIV infection is high, despite the implementation of TB control programs [2]. Furthermore, the increased prevalence of multidrug-resistant strains of M. tuberculosis represents a challenge for treatment programmes [3]. 10.1002/eji.200839115 Eur. J. Immunol. 2009Immunol. . 39: 1914Immunol. -1922 Johanneke Kleinnijenhuis et al. 1914The first line of defense against M. tuberculosis is formed by alveolar macrophages, which ingest and sequester the bacilli within granulomatous structures. The control and resolution of the infection involve the activation of macrophages, in which activated T lymphocytes play a crucial role [4]. The release of proinflammatory cytokines such as IL-1b, TNF, IL-12 or IL-18 from monocytes and monocyte-derived macrophages induces the production of T-cell-derived cytokines, most importantly IFN-g, which in turn will activate macrophages for the killing and elimination of the microorganisms [5,6]. Patients with defects in receptors for IL-12 and IFN have an increased susceptibility to mycobacterial infections [7][8][9], while the association between low CD4 counts and TB is well-known in HIV-infected patients [2].While most of the research has focused on the mechanisms resp...

show abstract

Caspase-1 Activation of IL-1β and IL-18 Are Essential for Shigella flexneri–Induced Inflammation

Cited by 368 publications

References 42 publications

Delivery of Biologically Active Anti-Inflammatory Cytokines IL-10 and IL-1ra In Vivo by the Shigella Type III Secretion Apparatus

Delivery of Biologically Active Anti-Inflammatory Cytokines IL-10 and IL-1ra In Vivo by the Shigella Type III Secretion Apparatus

IL-18 Levels and the Outcome of Innate Immune Response to Lipopolysaccharide: Importance of a Positive Feedback Loop with Caspase-1 in IL-18 Expression

Transcriptional and inflammasome‐mediated pathways for the induction of IL‐1β production by Mycobacterium tuberculosis

Contact Info

Product

Resources

About