A Tricky Diagnosis

Singh, Amarinder; Frazee, Brad; Talan, David A.; Ng, Valerie; Perez, Berenice

doi:10.1056/nejmcps1800926

Cited by 5 publications

(4 citation statements)

References 11 publications

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“…In comparison, a stable correlation in the survival burden of both adult worms and ML was found to be related to treatment with anti-rTs-serpin serum or rTs-serpin, and it was speculated to be mainly attributed to the change of immunoregulatory properties. In addition, in view of the short-term effectiveness of passive immunity on the immune response, the reduction in ML burden, which was consistent with the effects of the treatment strategies for T. spiralis infection reported previously, was considered to be caused by a decline in adult worms (43). Furthermore, because the upregulated IL-4 level was inhibited at 6 dpi, the immunoregulatory effect of rTs-serpin in the process of T. spiralis infection was supposed to be derived from immunosuppression rather than from the Th2-type immune response.…”

Section: Discussionsupporting

confidence: 84%

The Anti-Inflammatory Immune Response in Early Trichinella spiralis Intestinal Infection Depends on Serine Protease Inhibitor–Mediated Alternative Activation of Macrophages

Bai

Liu

et al. 2021

The Journal of Immunology

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Trichinella spiralis is recognized for its ability to regulate host immune responses via excretory/secretory (ES) products. Serine protease inhibitors (serpins) play an important role in ES product-mediated immunoregulatory effects during T. spiralis infection. In this study, the immunoregulatory properties of a serpin derived from T. spiralis (Ts-serpin) were explored in BALB/c mice. The results showed that naturally occurring Ts-serpin was detected in the stichosomes of muscle larvae and adult worms. Moreover, enhancing (by injection of a soluble-expressed recombinant Ts-serpin [rTs-serpin]) or blocking (by passive immunization with anti-rTs-serpin serum) the effects of Ts-serpin changed the levels of cytokines related to inflammation induced by T. spiralis infection in the serum, mesenteric lymph nodes, and peritoneal cavity, which then led to a change in the adult worm burden in early T. spiralis infection. Moreover, the phenotypic changes in peritoneal macrophages were found to be related to Ts-serpinmediated immunoregulation. Furthermore, a STAT6 activation mechanism independent of IL-4Ra has been found to regulate protein-mediated alternative activation of bone marrow-derived macrophages and mimic the immunoregulatory role of Ts-serpin in T. spiralis infection. Finally, the anti-inflammatory properties of rTs-serpin and bone marrow-derived macrophage alternative activation by rTs-serpin were demonstrated using a trinitrobenzene sulfonic acid-induced inflammatory bowel disease model. In summary, a protein-triggered anti-inflammatory mechanism was found to favor the survival of T. spiralis in the early stage of infection and help to elucidate the immunoregulatory effects of T. spiralis on the host immune response.

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Section: Discussionsupporting

confidence: 84%

The Anti-Inflammatory Immune Response in Early Trichinella spiralis Intestinal Infection Depends on Serine Protease Inhibitor–Mediated Alternative Activation of Macrophages

Bai

Liu

et al. 2021

The Journal of Immunology

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“…T. spiralis is accounts for serious economic losses in the pig industry and hundreds of human infections worldwide annually [2][3][4]. Domestic pork is the main source of human trichinellosis, which results from consumer ingestion of infectious meat [5,6]. In China, the southwestern, central and northeastern parts are the main endemic areas of T. spiralis infections in herds, which is consistent with the highest prevalence of human trichinellosis reported in Yunnan, Hubei and Henan provinces [7,8].…”

Section: Introductionsupporting

confidence: 58%

“…spiralis is accounts for serious economic losses in the pig industry and hundreds of human infections worldwide annually [ 2 – 4 ]. Domestic pork is the main source of human trichinellosis, which results from consumer ingestion of infectious meat [ 5 , 6 ]. In China, the southwestern, central and northeastern parts are the main endemic areas of T .…”

Section: Introductionmentioning

confidence: 99%

Recombinant cystatin-like protein-based competition ELISA for Trichinella spiralis antibody test in multihost sera

Liu

et al. 2021

PLoS Negl Trop Dis

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Objectives Trichinella spiralis is a zoonotic parasite with a complex parasitic life cycle and exposed to animals or humans by infectious meat. To control transmissions of T. spiralis through the food chain to humans, sensitive and selective multihost sera-diagnosis is urgent needed for monitoring T. spiralis exposure. Methods A competition enzyme-linked immunosorbent assay (cELISA) for T. spiralis infection diagnosis in multihost sera was developed based on recombinant cystatin-like protein (rCLP-cELISA) as well as monoclonal antibodies. The sensitivity and accuracy of the rCLP-cELISA were quantified using swine (n = 1316), mice (n = 189) and human (n = 157) serum samples. T. spiralis-antibody targeting test ability of the rCLP-cELISA in swine (n = 22) and human (n = 36), instead of other parasites or viruses antibodies, was evaluated. Results The rCLP-cELISA showed high agreement with commercial ELISA kits in field swine sera assessed by Cohen’s kappa value (κ = 0.7963). And it showed 100% specificity in human trichinellosis detection with sensitivity of 96.49%, no cross-reaction with other parasite or virus infections, and high positive detection rate of 87.5% in low-dose infected swine. Besides, the rCLP-cELISA exhibited potential in the detection of T. spiralis, T. nelsoni and Trichinella T8 infections. Conclusions The rCLP-cELISA can be used for T. spiralis-associated antibody test in multihost sera.

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“…Infections with pathogens (e.g., viruses and helminths) are important cause of mortality and morbidity in fibrosis [11][12][13][14][15]. Host immune response controls helminth infection but can lead to fibrosis when improperly controlled [16].…”

Section: Introductionmentioning

confidence: 99%

Akkermansia muciniphila participates in the host protection against helminth-induced cardiac fibrosis via TLR2

Wang,

Liu,

Sun

et al. 2023

PLoS Pathog

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Helminth Trichinella spiralis (Ts) is one of the major pathogens of human infective myocarditis that can lead to cardiac fibrosis (CF). The gut microbiota involved in this pathology are of interest. Here, we use mice infected with Ts as a model to examine the interactions between gut microbes and host protection to CF. Infected mice show enhanced CF severity. We find that antibiotics treatment to deplete the microbiota aggravates the disease phenotype. Attempts to restore microbiota using fecal microbiota transplantation ameliorates helminth-induced CF. 16S rRNA gene sequencing and metagenomics sequencing reveal a higher abundance of Akkermansia muciniphila in gut microbiomes of Ts-infected mice. Oral supplementation with alive or pasteurized A. muciniphila improves CF via TLR2. This work represents a substantial advance toward our understanding of causative rather than correlative relationships between the gut microbiota and CF.

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A Tricky Diagnosis

Cited by 5 publications

References 11 publications

The Anti-Inflammatory Immune Response in Early Trichinella spiralis Intestinal Infection Depends on Serine Protease Inhibitor–Mediated Alternative Activation of Macrophages

The Anti-Inflammatory Immune Response in Early Trichinella spiralis Intestinal Infection Depends on Serine Protease Inhibitor–Mediated Alternative Activation of Macrophages

Recombinant cystatin-like protein-based competition ELISA for Trichinella spiralis antibody test in multihost sera

Akkermansia muciniphila participates in the host protection against helminth-induced cardiac fibrosis via TLR2

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