scholarly journals Cellular and molecular changes and immune response in the intestinal mucosa during Trichinella spiralis early infection in rats

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
María Priscila Saracino ◽  
Cecilia Celeste Vila ◽  
Melina Cohen ◽  
María Virginia Gentilini ◽  
Guido Hernán Falduto ◽  
...  

Abstract Background: The main targets of the host’s immune system in Trichinella spiralis infection are the adult worms (AW), at the gut level, and the migrant or newborn larvae (NBL), at systemic and pulmonary levels. Most of the studies carried out in the gut mucosa have been performed on the Payer’s patches and/or the mesenteric lymph nodes but not on the lamina propria, therefore, knowledge on the gut immune response against T. spiralis remains incomplete. Methods This study aimed at characterizing the early mucosal immune response against T. spiralis, particularly, the events taking place between 1 and 13 dpi. For this purpose, Wistar rats were orally infected with muscle larvae of T. spiralis and the humoral and cellular parameters of the gut immunity were analysed, including the evaluation of the ADCC mechanism exerted by lamina propria cells. Results A marked inflammation and structural alteration of the mucosa was found. The changes involved an increase in goblet cells, eosinophils and mast cells, and B and T lymphocytes, initially displaying a Th1 profile, characterised by the secretion of IFN-γ and IL-12, followed by a polarization towards a Th2 profile, with a marked increase in IgE, IgG1, IL-4, IL-5 and IL-13 levels, which occurred once the infection was established. In addition, the helminthotoxic activity of lamina propria cells demonstrated the role of the intestine as a place of migrant larvae destruction, indicating that not all the NBLs released in the gut will be able to reach the muscles. Conclusions The characterization of the immune response triggered in the gut mucosa during T. spiralis infection showed that not only an effector mechanism is directed toward the AW but also towards the NBL as a cytotoxic activity was observed against NBL exerted by lamina propria cells.

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 437 ◽  
Author(s):  
Yao Zhang ◽  
Jie Zeng ◽  
Yan Yan Song ◽  
Shao Rong Long ◽  
Ruo Dan Liu ◽  
...  

Trichinella spiralis is a major foodborne parasite and has a serious threat to meat safety. Development of anti-Trichinella vaccines is prospective to eliminate Trichinella infection in food animal. The aim of this study was to assess the biological properties of a novel T. spiralis trypsin (TsT) and its elicited immune protection against larval challenge. The cDNA sequence of TsT gene was cloned and expressed. Western blotting showed rTsT was identified by infection serum and anti-TsT serum. RT-PCR results revealed that TsT gene was transcribed at diverse T. spiralis lifecycle stages. The IIFT results showed that natural TsT was principally expressed at epicuticle of 5-6 day adult worms, indicating that TsT is a worm somatic antigen and adult-stage specific surface antigen. Vaccination of mice with rTsT triggered an evident humoral immune response (high levels of serum IgG, IgG1/IgG2a, and enteral sIgA), and it also induced the systemic and enteral local cellular immune response, demonstrated by an significantly elevation of cytokines IFN-γ and IL-4. The mice vaccinated with rTsT exhibited a 33.17% reduction of enteral adult worms and a 37.80% reduction of muscle larvae after larval challenge. The results showed that TsT might be considered as a candidate target antigen for anti-T. spiralis vaccines.


PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e107933 ◽  
Author(s):  
Renata Curciarello ◽  
Alison Steele ◽  
Dianne Cooper ◽  
Thomas T. MacDonald ◽  
Laurens Kruidenier ◽  
...  

2015 ◽  
Vol 411 (1-2) ◽  
pp. 341-349 ◽  
Author(s):  
Giuseppe Iacomino ◽  
Angela Marano ◽  
Ilaria Stillitano ◽  
Vera Rotondi Aufiero ◽  
Gaetano Iaquinto ◽  
...  

Author(s):  
Tong Xu Zhuo ◽  
Zhen Wang ◽  
Yan Yan Song ◽  
Shu Wei Yan ◽  
Ruo Dan Liu ◽  
...  

Trichinella spiralis is a major foodborne parasite worldwide. After the encapsulated muscle larvae (ML) in meat are ingested, the ML are liberated in the stomach of the host and activated into intestinal infectious larvae (IIL), which develop into adult worm after molting four times. A novel glutamine synthetase (TsGS) was identified from T. spiralis IIL at 10 h post-infection, but its biological role in T. spiralis life cycle is not clear. The aim of this study was to investigate the biological characteristics of TsGS and its functions in larval acid resistance, molting, and development. TsGS has a glutamine synthetase (GS) catalytic domain. Complete TsGS sequence was cloned and expressed in Escherichia coli BL21. rTsGS has good immunogenicity. qPCR and Western blotting showed that TsGS was highly expressed at IIL stage, and immunofluorescence revealed that TsGS was principally localized at the cuticle and intrauterine embryos of this nematode. rTsGS has enzymatic activity of natural GS to hydrolyze the substrate (Glu, ATP, and NH4+). Silencing of TsGS gene significantly reduced the IIL survival at pH 2.5, decreased the IIL burden, and impeded larval molting and development. The results demonstrated that TsGS participates in T. spiralis larval acid resistance, molting and development, and it might be a candidate vaccine target against Trichinella molting and development.


Author(s):  
Loreto Gesualdo ◽  
Vincenzo Di Leo ◽  
Rosanna Coppo

Abstract The precise pathogenesis of immunoglobulin A nephropathy (IgAN) is still not clearly established but emerging evidence confirms a pivotal role for mucosal immunity. This review focuses on the key role of mucosa-associated lymphoid tissue (MALT) in promoting the onset of the disease, underlying the relationship among microbiota, genetic factors, food antigen, infections, and mucosal immune response. Finally, we evaluate potential therapies targeting microbes and mucosa hyperresponsiveness in IgAN patients.


2020 ◽  
Author(s):  
E Niccolai ◽  
E Russo ◽  
S Baldi ◽  
F Ricci ◽  
G Nannini ◽  
...  

ABSTRACTBackgroundColorectal cancer (CRC) is a widespread disease that represents an example of chronic inflammation-associated tumor. In fact, the immune system, besides protecting the host from developing tumors, can support the CRC progression. In this scenario, the gut microbiota (GM) is essential to modulate immune responses and a dysbiotic condition can favor chronic/abnormal immune activation that support the tumor growth. GM can elicit the production of cytokines, influencing the immunostimulatory or immunosuppressive reactions, such as the tendency to mount Th1, Th17, Tregs or Th9 responses that play different roles towards colon cancer. Paradigmatic is the role of IL-9 that can both promote tumor progression in hematological malignancies and inhibit tumorigenesis in solid cancers. Therefore, to investigate the microbiota-immunity axis in CRC patients is crucial to well understand the cancer development with positive relapses in prevention and treatment.AimThe cellular and molecular characterization of the immune response and the evaluation of GM composition in healthy and tumor mucosa, focusing on the correlation between cytokines’ profile and GM signature.MethodsWe collected tumoral (CRC) and healthy (CRC-S) mucosa samples of 45 CRC patients. For each sample, we characterized the Tissue Infiltrating Lymphocytes (TIL)’s subset profile and the GM composition. In addition, in 14 CRC patients, we evaluated the CRC and CRC-S molecular inflammatory response (26 cytokines/chemokines) and we correlated this profile with GM composition using the Dirichlet Multinomial Regression.ResultsThe analysis of T cells subsets distribution showed that CRC samples displayed higher percentages of Th17, Th2, Tregs, Tc17, Tc1/Tc17, and Tcreg, compared to CRC-S. Notably, also the number of Th9 was higher, even if not significantly, in CRC tissue compared to healthy one. In addition, we found that MIP-1α, IL-1β, IL-2, IP-10, IL-6, IL-8, IL-17A, IFN-γ, TNF-α, MCP-1, IL-1α, P-selectin and IL-9 were significantly increased in CRC compared to CRC-S. Moreover, the GM analysis revealed that CRC samples had significantly higher levels of Fusobacteria, Proteobacteria, Fusobacterium, Ruminococcus2 (Lachnospiraceae family) and Ruminococcus (Ruminococcaceae family) than CRC-S. Finally, we found that the abundance of Prevotella spp in CRC samples was negatively correlated with IL-17A and positively with IL-9. In addition, the abundance of Bacteroides and Escherichia/Shigella species in CRC samples showed a negative association with IL-9 and IP-10 respectively.ConclusionsOur data show a clear dissimilarity of inflammatory profile and GM composition between the tumor and the adjacent healthy tissue, displaying the generation of a peculiar CRC microenvironment. Interestingly, relating the tissue cytokine profile with the GM composition, we confirmed the presence of a bidirectional crosstalk between the immune response and the host’s commensal microorganisms; in detail, we documented for the first time that Prevotella spp. and Bacteroides spp. are correlated (positively and negatively, respectively) with the IL-9, whose role in CRC development is still debated.


Parasitology ◽  
2000 ◽  
Vol 121 (5) ◽  
pp. 565-573 ◽  
Author(s):  
J. PÉREZ-SERRANO ◽  
J. MARTÍNEZ ◽  
P. REGAL ◽  
W. E. BERNADINA ◽  
F. RODRÍGUEZ-CAABEIRO

We recently showed that, in our Trichinella spiralis rat model, first exposure, but not re-exposure to infective-stage larvae evoked heat shock responses in 4 test organs. Our work, however, failed to implicate either early complete clearance of challenge muscle larvae (ML), or rapid elimination of newborn larvae (NBL) in the phenomenon noted in reinfected rats. This study clarifies that issue using 2 established facts in T. spiralis biology and anti-T. spiralis immunology. That is, adult worms injure gut cells and immune destruction of NBL requires release of material also toxic to host cells. To approach the above problem we analysed relevant and irrelevant rat organs for increased heat shock protein (HSP) production at 1, 7, 14, 20 and 27 p.i. during first and second infections. Organs examined were intestines, mesenteric lymph nodes (MLN), heart and lungs. Using densitometric analyses of immunoblots, increased HSP expression was detected on day 7 in intestines from both primary and secondary-infected rats albeit that the change in the latter was just short of significant. Interestingly, MLN only exhibited increased HSP levels in the reinfected rat model with increased HSP levels persisting for 1 week. A lasting shock response was detected in reinfected rats; in contrast, first exposure resulted in shock responses being evident in lungs at either day 7 or day 14, only. These findings suggest that (i) in immune rats, a few challenge ML develop into adults, produce NBLwhich are trapped within MLN, and (ii) that anti-T. spiralis and/or anti-NBL immunity is associated with an, as yet, uncomprehended stress to host's heart tissues.


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