scholarly journals IL-13 promotes recovery from C. difficile infection

2021 ◽  
Author(s):  
Alexandra N Donlan ◽  
Jhansi L Leslie ◽  
Morgan E Simpson ◽  
William A Petri ◽  
Judith E Allen ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Clinical Score ◽  
Protective Role ◽  
Lymphoid Cells ◽  
M2 Macrophage ◽  
Hospital Acquired Infection ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Hospital Acquired

Clostridioides difficile infection (CDI) is the leading hospital-acquired infection in North America. We have previously discovered that antibiotic disruption of the gut microbiota decreases intestinal IL-33 and IL-25 and increases susceptibility to CDI. We further found that IL-33 promotes protection through type 2 Innate Lymphoid Cells (ILC2s), which produce IL-13. However, the contribution of IL-13 to disease has never been explored. We found that administration of IL-13 protected, and anti-IL-13 exacerbated CDI as measured by weight loss and clinical score, particularly during disease resolution. Additionally, concordant with IL-13 being important for M2 macrophage polarization, we saw a decrease in M2 macrophages (CD11B+CD64+CD206+) cells following neutralization of IL-13. We also observed monocyte accumulation as early as day three post-infection following IL-13 neutralization, suggesting IL-13 may be directly or indirectly important for their recruitment or transition into macrophages. Neutralization of the decoy receptor IL-13Rα2 resulted in protection from disease, likely through increased available endogenous IL-13. Our data highlight the protective role of IL-13 in promoting recovery from CDI and the association of poor responses with a dysregulated monocyte-macrophage compartment. These results increase our understanding of type 2 immunity in CDI and may have implications for treating disease in patients.

Using diagnostic stewardship to reduce rates, healthcare expenditures and accurately identify cases of hospital-onset Clostridioides difficile infection

2020 ◽  
Vol 42 (1) ◽  
pp. 51-56
Author(s):  
Dipesh Solanky ◽  
Derek K. Juang ◽  
Scott T. Johns ◽  
Ian C. Drobish ◽  
Sanjay R. Mehta ◽  
...  
Keyword(s):  
Healthcare Facility ◽  
Nucleic Acid Amplification ◽  
Fiscal Year ◽  
Hospital Acquired Infection ◽  
Laxative Use ◽  
Clostridioides Difficile ◽  
Hospitalization Costs ◽  
Clostridioides Difficile Infection ◽  
Hospital Acquired ◽  
Hospital Days

AbstractObjective:Lack of judicious testing can result in the incorrect diagnosis of Clostridioides difficile infection (CDI), unnecessary CDI treatment, increased costs and falsely augmented hospital-acquired infection (HAI) rates. We evaluated facility-wide interventions used at the VA San Diego Healthcare System (VASDHS) to reduce healthcare-onset, healthcare-facility–associated CDI (HO-HCFA CDI), including the use of diagnostic stewardship with test ordering criteria.Design:We conducted a retrospective study to assess the effectiveness of measures implemented to reduce the rate of HO-HCFA CDI at the VASDHS from fiscal year (FY)2015 to FY2018.Interventions:Measures executed in a stepwise fashion included a hand hygiene initiative, prompt isolation of CDI patients, enhanced terminal room cleaning, reduction of fluoroquinolone and proton-pump inhibitor use, laboratory rejection of solid stool samples, and lastly diagnostic stewardship with C. difficile toxin B gene nucleic acid amplification testing (NAAT) criteria instituted in FY2018.Results:From FY2015 to FY2018, 127 cases of HO-HCFA CDI were identified. All rate-reducing initiatives resulted in decreased HO-HCFA cases (from 44 to 13; P ≤ .05). However, the number of HO-HCFA cases (34 to 13; P ≤ .05), potential false-positive testing associated with colonization and laxative use (from 11 to 4), hospital days (from 596 to 332), CDI-related hospitalization costs (from $2,780,681 to $1,534,190) and treatment cost (from $7,158 vs $1,476) decreased substantially following the introduction of diagnostic stewardship with test criteria from FY2017 to FY2018.Conclusions:Initiatives to decrease risk for CDI and diagnostic stewardship of C. difficile stool NAAT significantly reduced HO-HCFA CDI rates, detection of potential false-positives associated with laxative use, and lowered healthcare costs. Diagnostic stewardship itself had the most dramatic impact on outcomes observed and served as an effective tool in reducing HO-HCFA CDI rates.

scholarly journals The interplay of SARS-CoV-2 and Clostridioides difficile infection

2021 ◽  
Vol 16 (6) ◽  
pp. 439-443
Author(s):  
Sahil Khanna ◽  
Colleen S Kraft
Keyword(s):  
High Risk ◽  
Infection Control ◽  
Gastrointestinal Symptoms ◽  
Control Measures ◽  
Antibiotic Exposure ◽  
Hospital Acquired Infections ◽  
Infection Control Measures ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Hospital Acquired

The COVID-19 pandemic has changed the way we practice medicine and lead our lives. In addition to pulmonary symptoms; COVID-19 as a syndrome has multisystemic involvement including frequent gastrointestinal symptoms such as diarrhea. Due to microbiome alterations with COVID-19 and frequent antibiotic exposure, COVID-19 can be complicated by Clostridioides difficile infection. Co-infection with these two can be associated with a high risk of complications. Infection control measures in hospitals is enhanced due to the COVID-19 pandemic which in turn appears to reduce the incidence of hospital-acquired infections such as C. difficile infection. Another implication of COVID-19 and its potential transmissibility by stool is microbiome-based therapies. Potential stool donors should be screened COVID-19 symptoms and be tested for COVID-19.

scholarly journals Potentiating Tissue-Resident Type 2 Innate Lymphoid Cells by IL-33 to Prevent Renal Ischemia-Reperfusion Injury

2018 ◽  
Vol 29 (3) ◽  
pp. 961-976 ◽  
Author(s):  
Qi Cao ◽  
Yiping Wang ◽  
Zhiguo Niu ◽  
Chengshi Wang ◽  
Ruifeng Wang ◽  
...  
Keyword(s):  
Protective Effect ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Lymphoid Cells ◽  
M2 Macrophages ◽  
Humanized Mouse Model

The IL-33-type 2 innate lymphoid cell (ILC2) axis has an important role in tissue homeostasis, inflammation, and wound healing. However, the relative importance of this innate immune pathway for immunotherapy against inflammation and tissue damage remains unclear. Here, we show that treatment with recombinant mouse IL-33 prevented renal structural and functional injury and reduced mortality in mice subjected to ischemia-reperfusion injury (IRI). Compared with control-treated IRI mice, IL-33–treated IRI mice had increased levels of IL-4 and IL-13 in serum and kidney and more ILC2, regulatory T cells (Tregs), and anti-inflammatory (M2) macrophages. Depletion of ILC2, but not Tregs, substantially abolished the protective effect of IL-33 on renal IRI. Adoptive transfer of ex vivo–expanded ILC2 prevented renal injury in mice subjected to IRI. This protective effect associated with induction of M2 macrophages in kidney and required ILC2 production of amphiregulin. Treatment of mice with IL-33 or ILC2 after IRI was also renoprotective. Furthermore, in a humanized mouse model of renal IRI, treatment with human IL-33 or transfer of ex vivo–expanded human ILC2 ameliorated renal IRI. This study has uncovered a major protective role of the IL-33–ILC2 axis in renal IRI that could be potentiated as a therapeutic strategy.

scholarly journals Protective Role of C3aR (C3a Anaphylatoxin Receptor) Against Atherosclerosis in Atherosclerosis-Prone Mice

2020 ◽  
Vol 40 (9) ◽  
pp. 2070-2083
Author(s):  
Lin-Lin Wei ◽  
Ning Ma ◽  
Kun-Yi Wu ◽  
Jia-Xing Wang ◽  
Teng-Yue Diao ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Protective Role ◽  
Plaque Burden ◽  
Aortic Tissue ◽  
M2 Macrophage ◽  
Proinflammatory Mediators ◽  
Anti Inflammatory

Objective: Emerging evidence suggests that C3aR (C3a anaphylatoxin receptor) signaling has protective roles in various inflammatory-related diseases. However, its role in atherosclerosis has been unknown. The purpose of the study was to investigate the possible protective role of C3aR in aortic atherosclerosis and explore molecular and cellular mechanisms involved in the protection. Approach and Results: C3ar −/− /Apoe −/− mice were generated by cross-breeding of atherosclerosis-prone Apoe −/− mice and C3ar −/− mice. C3ar −/− /Apoe −/− mice and Apoe −/− mice (as a control) underwent high-fat diet for 16 weeks were assessed for (1) atherosclerotic plaque burden, (2) aortic tissue inflammation, (3) recruitment of CD11b + leukocytes into atherosclerotic lesions, and (4) systemic inflammatory responses. Compared with Apoe −/− mice, C3ar −/− /Apoe −/− mice developed more severe atherosclerosis. In addition, C3ar −/− /Apoe −/− mice have increased local production of proinflammatory mediators (eg, CCL2 [chemokine (C-C motif) ligand 2], TNF [tumor necrosis factor]-α) and infiltration of monocyte/macrophage in aortic tissue, and their lesional macrophages displayed an M1-like phenotype. Local pathological changes were associated with enhanced systemic inflammatory responses (ie, elevated plasma levels of CCL2 and TNF-α, increased circulating inflammatory cells). In vitro analyses using peritoneal macrophages showed that C3a stimulation resulted in upregulation of M2-associated signaling and molecules, but suppression of M1-associated signaling and molecules, supporting the roles of C3a/C3aR axis in mediating anti-inflammatory response and promoting M2 macrophage polarization. Conclusions: Our findings demonstrate a protective role for C3aR in the development of atherosclerosis and suggest that C3aR confers the protection through C3a/C3aR axis–mediated negative regulation of proinflammatory responses and modulation of macrophage toward the anti-inflammatory phenotype.

Hospital acquired Clostridioides difficile infection and risk factors for severity in a university hospital: A prospective study

2020 ◽  
Vol 48 (12) ◽  
pp. 1426-1430
Author(s):  
Hüseyin Bilgin ◽  
Elvan Sayın ◽  
Hande Perk Gürün ◽  
Elif Tükenmez-Tigen ◽  
Nurver Ülger Toprak ◽  
...  
Keyword(s):  
Risk Factors ◽  
Prospective Study ◽  
University Hospital ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
A Prospective Study ◽  
Hospital Acquired

scholarly journals Macrophage Polarization Modulated by Porcine Circovirus Type 2 Facilitates Bacterial Coinfection

2021 ◽  
Vol 12 ◽  
Author(s):  
Wen Zhang ◽  
Zhendong Fu ◽  
Hongyan Yin ◽  
Qingbing Han ◽  
Wenhui Fan ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Porcine Circovirus Type ◽  
Porcine Circovirus Type 2 ◽  
Pcv2 Infection ◽  
Porcine Circovirus ◽  
Economic Losses ◽  
Target Cells ◽  
M2 Macrophage ◽  
Bacterial Coinfection

Polarization of macrophages to different functional states is important for mounting responses against pathogen infections. Macrophages are the major target cells of porcine circovirus type 2 (PCV2), which is the primary causative agent of porcine circovirus–associated disease (PCVAD) leading to immense economic losses in the global swine industry. Clinically, PCV2 is often found to increase risk of other pathogenic infections yet the underlying mechanisms remain to be elusive. Here we found that PCV2 infection skewed macrophages toward a M1 status through reprogramming expression of a subset of M1-associated genes and M2-associated genes. Mechanistically, induction of M1-associated genes by PCV2 infection is dependent on activation of nuclear factor kappa B (NF-κB) and c-jun N-terminal kinase (JNK) signaling pathways whereas suppression of M2-associated genes by PCV2 is via inhibiting expression of jumonji domain containing-3 (JMJD3), a histone 3 Lys27 (H3K27) demethylase that regulates M2 activation of macrophages. Finally, we identified that PCV2 capsid protein (Cap) directly inhibits JMJD3 transcription to restrain expression of interferon regulatory factor (IRF4) that controls M2 macrophage polarization. Consequently, sustained infection of PCV2 facilitates bacterial infection in vitro. In summary, these findings showed that PCV2 infection functionally modulated M1 macrophage polarization via targeting canonical signals and epigenetic histone modification, which contributes to bacterial coinfection and virial pathogenesis.

scholarly journals Bactericidal and Bacteriostatic Antibiotics

2021 ◽  
Author(s):  
Sachin M. Patil ◽  
Parag Patel
Keyword(s):  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Vital Role ◽  
Mortality And Morbidity ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Multiple Trials ◽  
Outpatient Settings ◽  
Red Dye ◽  
Hospital Acquired

Of all the medications available to physicians worldwide, antibiotics play an essential role in inpatient and outpatient settings. Discovered in the early nineteenth century by Alexander Fleming, penicillin was the first antibiotic isolated from a mold. Dr. Gerhard Domagk developed synthetic sulfa drugs by altering the red dye used in chemical industries. Since then, multiple antibiotic classes have been discovered with varying antimicrobial effects enabling their use empirically or in specific clinical scenarios. Antibiotics with different mechanisms of action could be either bactericidal or bacteriostatic. However, no clinical significance has been observed between cidal and static antibiotics in multiple trials. Their presence has led to safer deep invasive surgeries, advanced chemotherapy in cancer, and organ transplantation. Indiscriminate usage of antibiotics has resulted in severe hospital-acquired infections, including nosocomial pneumonia, Clostridioides difficile infection, multidrug-resistant invasive bacterial infections, allergic reactions, and other significant side effects. Antibiotic stewardship is an essential process in the modern era to advocate judicial use of antibiotics for an appropriate duration. They play a vital role in medical and surgical intensive care units to address the various complications seen in these patients. Antibiotics are crucial in severe acute infections to improve overall mortality and morbidity.

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