The Role of Toll-Like Receptor-2 in Clostridioides difficile Infection: Evidence From a Mouse Model and Clinical Patients

Lai, Ying‐Huang; Tsai, Bo‐Yang; Hsu, Chih-Yu; Chen, Yi‐Hsuan; Chou, Po-Han; Chen, Yueh-Lin; Liu, Hsiao-Chieh; Ko, Wen–Chien; Tsai, Pei-Jane; Hung, Yuan‐Pin

doi:10.3389/fimmu.2021.691039

Cited by 9 publications

(12 citation statements)

References 41 publications

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“…Based on this observation, it was evident that toxoiding had no effect on the ability of CP26 to enhance IFNγ transcription, while TLR21 expression in macrophages required the neutralization of toxin activity in the secreted component. Previous reports have shown that secreted factors such as alpha-toxin from C. perfringens (gas gangrene strain), binary toxin (CDT) from Clostridioides difficile, or type III secretion factors from Gram negative bacteria can trigger TLR-mediated recognition in immune cells to induce an inflammatory response [26][27][28][29]. To this end, further studies are essential to determine which of the secreted factors can specifically target macrophage activation machinery.…”

Section: Discussionmentioning

confidence: 99%

Avian Macrophage Responses to Virulent and Avirulent Clostridium perfringens

2022

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The present study evaluated the avian macrophage responses against Clostridium perfringens that varied in their ability to cause necrotic enteritis in chickens. Strains CP5 (avirulent-netB+), CP1 (virulent-netB+), and CP26 (highly virulent-netB+tpeL+) were used to evaluate their effect on macrophages (MQ-NCSU cells) and primary splenic and cecal tonsil mononuclear cells. The bacilli (whole cells) or their secretory products from all three strains induced a significant increase in the macrophage transcription of Toll-like receptor (TLR)21, TLR2, interleukin (IL)-1β, inducible nitric oxide synthase (iNOS), and CD80 genes as well as their nitric oxide (NO) production and major histocompatibility complex (MHC)-II surface expression compared to an unstimulated control. The CP1 and CP26-induced expression of interferon (IFN)γ, IL-6, CD40 genes, MHC-II upregulation, and NO production was significantly higher than that of CP5 and control groups. Furthermore, splenocytes and cecal tonsillocytes stimulated with bacilli or secretory products from all the strains showed a significant increase in the frequency of macrophages, their surface expression of MHC-II and NO production, while CP26-induced responses were significantly higher for the rest of the groups. In summary, macrophage interaction with C. perfringens can lead to cellular activation and, the ability of this pathogen to induce macrophage responses may depend on its level of virulence.

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Section: Discussionmentioning

confidence: 99%

Avian Macrophage Responses to Virulent and Avirulent Clostridium perfringens

2022

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“…As mentioned, several host factors affect immunity status, such as age, underlying hematologic malignancy, and immune gene polymorphisms, and influence protective immunity during CDIs. 1 , 4 , 5 In the clinical study in Iran, the receipt of anti-tumor necrosis factor (TNF)-containing regimens in combinations with other immunosuppressive medications may impact the susceptibility to CDI among patients with underlying inflammatory bowel disease. 20 Immunosuppressant drugs might predispose relatively non-immunocompetent patients to develop, instead of protect from, CDI.…”

Section: Discussionmentioning

confidence: 99%

“…Clostridioides difficile is well known to cause gastrointestinal infections, ranging from mild diarrhea to pseudomembranous colitis or toxic megacolon. 1–3 Because innate immunity plays a crucial role in the occurrence and development of C. difficile infections (CDIs), 1 , 4 impaired host immunity, such as the presence of hematological malignancy or polymorphisms of immune genes (such as IL-8 or toll-like receptors), is linked to the increased incidence and recurrence rates of CDIs. 1 , 4 , 5 …”

Section: Introductionmentioning

confidence: 99%

“…Clostridioides difficile is well known to cause gastrointestinal infections, ranging from mild diarrhea to pseudomembranous colitis or toxic megacolon. [1][2][3] Because innate immunity plays a crucial role in the occurrence and development of C. difficile infections (CDIs), 1,4 impaired host immunity, such as the presence of hematological malignancy or polymorphisms of immune genes (such as IL-8 or toll-like receptors), is linked to the increased incidence and recurrence rates of CDIs. 1,4,5 The association between immunosuppressant drugs and the occurrence or development of CDIs is ambiguous and seems to be one body two sides.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] Because innate immunity plays a crucial role in the occurrence and development of C. difficile infections (CDIs), 1,4 impaired host immunity, such as the presence of hematological malignancy or polymorphisms of immune genes (such as IL-8 or toll-like receptors), is linked to the increased incidence and recurrence rates of CDIs. 1,4,5 The association between immunosuppressant drugs and the occurrence or development of CDIs is ambiguous and seems to be one body two sides. [6][7][8][9][10][11][12] In the past, recent immunosuppressant usage (within six months) has been recognized as an independent risk factor for asymptomatic carriage of C. difficile.…”

Section: Introductionmentioning

confidence: 99%

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Impacts of Corticosteroid Therapy at Acute Stage of Hospital-Onset Clostridioides difficile Infections

Lee¹,

Lee²,

Chiu³

et al. 2022

IDR

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Introduction The influence of corticosteroid therapy before or after the onset of Clostridioides difficile infections (CDIs) on the clinical outcomes of adults with hospital-onset CDIs was investigated. Materials and Methods A clinical study was conducted on the medical wards of a teaching hospital between January 2013 and April 2020. Adults (aged ≥ 20 years) with hospital-onset CDIs (ie, symptom onset at least 48 hours after hospitalization) were included. “Corticosteroid therapy during acute CDIs” was defined as the receipt of a corticosteroid at the prednisolone equivalent (PE) dose of ≥10 mg for at least 48 hours within one week after the CDI diagnosis. “Prior corticosteroid exposure” was defined as the receipt of a corticosteroid at the PE dose of ≥5 mg PE for at least 48 hours within one month before the CDI diagnosis. Results Of the 243 adults with hospital-onset CDIs, patients (44, 18.1%) who received corticosteroid therapy during acute CDIs were more likely to have prior corticosteroid exposure (86.4% vs 11.9%, P <0.001) and CDI episodes in intensive care units (31.8% vs 10.8%, P =0.001). Of note, a crucial association between corticosteroid therapy during acute CDIs and CDI recurrence was evidenced (13.6% vs 1.5%, P =0.002). Prior corticosteroid exposure was not associated with favorable CDI outcomes in terms of successful treatment (78.3% vs 74.9%, P =0.89), in-hospital crude mortality (17.4% vs 24.0%, P =0.61), or CDI recurrence (4.3% vs 5.3%, P = 1.00). However, for 177 patients without prior corticosteroid exposure, corticosteroid therapy during acute CDIs was linked to a higher proportion of CDI recurrence (33.3% vs 5.3%, P =0.046). Conclusion Corticosteroid therapy during acute CDIs might impact the recurrence of CDIs, particularly in those with a lack of prior corticosteroid exposure.

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Mouse models for bacterial enteropathogen infections: insights into the role of colonization resistance

et al. 2023

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Globally, enteropathogenic bacteria are a major cause of morbidity and mortality. 1-3 Campylobacter, Salmonella , Shiga-toxin-producing Escherichia coli , and Listeria are among the top five most commonly reported zoonotic pathogens in the European Union. 4 However, not all individuals naturally exposed to enteropathogens go on to develop disease. This protection is attributable to colonization resistance (CR) conferred by the gut microbiota, as well as an array of physical, chemical, and immunological barriers that limit infection. Despite their importance for human health, a detailed understanding of gastrointestinal barriers to infection is lacking, and further research is required to investigate the mechanisms that underpin inter-individual differences in resistance to gastrointestinal infection. Here, we discuss the current mouse models available to study infections by non-typhoidal Salmonella strains, Citrobacter rodentium (as a model for enteropathogenic and enterohemorrhagic E. coli), Listeria monocytogenes , and Campylobacter jejuni. Clostridioides difficile is included as another important cause of enteric disease in which resistance is dependent upon CR. We outline which parameters of human infection are recapitulated in these mouse models, including the impact of CR, disease pathology, disease progression, and mucosal immune response. This will showcase common virulence strategies, highlight mechanistic differences, and help researchers from microbiology, infectiology, microbiome research, and mucosal immunology to select the optimal mouse model.

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The Role of Toll-Like Receptor-2 in Clostridioides difficile Infection: Evidence From a Mouse Model and Clinical Patients

Cited by 9 publications

References 41 publications

Avian Macrophage Responses to Virulent and Avirulent Clostridium perfringens

Avian Macrophage Responses to Virulent and Avirulent Clostridium perfringens

Impacts of Corticosteroid Therapy at Acute Stage of Hospital-Onset Clostridioides difficile Infections

Mouse models for bacterial enteropathogen infections: insights into the role of colonization resistance

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