scholarly journals Innate Immune Responses Associated with Resistance against Haemonchus contortus in Morada Nova Sheep

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
João Henrique Barbosa Toscano ◽  
Cintia Hiromi Okino ◽  
Isabella Barbosa dos Santos ◽  
Luciana Aparecida Giraldelo ◽  
Marei Borsch von Haehling ◽  
...  

The immune response against Haemonchus contortus infections is primarily associated with the Th2 profile. However, the exact mechanisms associated with increased sheep resistance against this parasite remains poorly elucidated. The present study is aimed at evaluating mediators from the innate immune response in lambs of the Morada Nova Brazilian breed with contrasting H. contortus resistance phenotypes. Briefly, 287 lambs were characterized through fecal egg counts (FEC) and packed cell volume (PCV) after two independent experimental parasitic challenges with 4,000 H. contortus L3. 20 extreme resistance phenotypes (10 most resistant and 10 most susceptible) were selected, subjected to a third artificial infection with 4,000 L3, and euthanized 7 days later. Tissue samples were collected from abomasal fundic and pyloric mucosa and abomasal lymph nodes. Blood samples were collected at days 0 and 7 of the third parasitic challenge. RNA was extracted from tissue and blood samples for relative quantification of innate immune-related genes by RT-qPCR. For the abomasal fundic mucosa, increased TNFα and IL1β expression levels (P<0.05) were found in the susceptible animals, while resistant animals had IL33 superiorly expressed (P<0.05). Higher levels (P<0.05) of TLR2 and CFI were found in the abomasal pyloric mucosa of resistant animals. TNFα was at higher levels (P<0.05) in the blood of susceptible lambs, at day 0 of the third artificial infection. The exacerbated proinflammatory response observed in susceptible animals, at both local and systemic levels, may be a consequence of high H. contortus parasitism. This hypothesis is corroborated by the higher blood levels of TNFα before the onset of infection, which probably remained elevated from the previous parasitic challenges. On the other hand, resistant lambs had an enhanced response mediated by TLR recognition and complement activation. Nevertheless, this is the first study to directly associate sheep parasitic resistance with IL33, an innate trigger of the Th2-polarized response.

2012 ◽  
Vol 80 (8) ◽  
pp. 2905-2913 ◽  
Author(s):  
Jessica Queen ◽  
Karla J. Fullner Satchell

ABSTRACTCholera is classically considered a noninflammatory diarrheal disease, in comparison to invasive enteric organisms, although there is a low-level proinflammatory response during early infection withVibrio choleraeand a strong proinflammatory reaction to live attenuated vaccine strains. Using an adult mouse intestinal infection model, this study examines the contribution of neutrophils to host defense to infection. Nontoxigenic El Tor O1V. choleraeinfection is characterized by the upregulation of interleukin-6 (IL-6), IL-10, and macrophage inflammatory protein 2 alpha in the intestine, indicating an acute innate immune response. Depletion of neutrophils from mice with anti-Ly6G IA8 monoclonal antibody led to decreased survival of mice. The role of neutrophils in protection of the host is to limit the infection to the intestine and control bacterial spread to extraintestinal organs. In the absence of neutrophils, the infection spread to the spleen and led to increased systemic levels of IL-1β and tumor necrosis factor alpha, suggesting the decreased survival in neutropenic mice is due to systemic shock. Neutrophils were found not to contribute to either clearance of colonizing bacteria or to alter the local immune response. However, when genes for secreted accessory toxins were deleted, the colonizing bacteria were cleared from the intestine, and this clearance is dependent upon neutrophils. Thus, the requirement for accessory toxins in virulence is negated in neutropenic mice, which is consistent with a role of accessory toxins in the evasion of innate immune cells in the intestine. Overall, these data support that neutrophils impact disease progression and suggest that neutrophil effectiveness can be manipulated through the deletion of accessory toxins.


2017 ◽  
Vol 745 ◽  
pp. 50-61 ◽  
Author(s):  
Razvan Adam ◽  
Horia Orban ◽  
Elisa Plopeanu ◽  
Dan Voinescu ◽  
Adrian Barbilian

Biodegradable magnesium-based alloys shows good prospects in their use as biodegradable orthopedic materials. The aim of this study is to demonstrate good biocompatibility and lack of local and systemic toxicity of some experimental implants made by magnesium alloy type Mg-Ca 0,8 [%wt]. The study was conducted by implanting some experimental pins made by magnesium alloy type Mg-Ca 0,8 [%wt] in bone, proximal femur and intramedullary tibia, and in thigh muscle of the rabbits. Also, we follow the evolution of blood levels of Mg, Ca, blood counts, liver and kidney function. The evolution of the experience animals was followed for 6 weeks by radiologic imaging, and taking blood samples. After 6 weeks, we obtain after euthanasia of animal experience the harvest blood samples, and musculoskeletal tissue samples for histopathological examination. The histopathology results have not demonstrated peri-implant cytotoxicity, bone and muscle cells being viable. Fibrosis at tissue implant border was minimal showing a good integration. There were no pathological increases in blood levels of Mg and Ca, or changes in blood counts, as well as no change in renal or hepatic function. All this experimental results demonstrates that the magnesium alloy type Mg-Ca 0,8 [%wt] represent a promising solution in orthopedic surgery, proving to be safe, with a high degree of biocompatibility, and without toxic effects.


Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 274 ◽  
Author(s):  
Tapas Patra ◽  
Ratna Ray ◽  
Ranjit Ray

Innate immune responses generate interferons, proinflammatory cytokines, complement activation, and natural killer (NK) cell response. Ultimately, this leads to the induction of a robust virus-specific adaptive immunity. Although the host innate immune system senses and responds to eliminate virus infection, hepatitis C virus (HCV) evades immune attack and establishes persistent infection within the liver. Spontaneous clearance of HCV infection is associated with a prompt induction of innate immunity generated in an infected host. In this review, we have highlighted the current knowledge of our understanding of host–HCV interactions, especially for endogenous interferon production, proinflammatory response, NK cell response, and complement activation, which may impair the generation of a strong adaptive immune response for establishment of chronicity. The information may provide novel strategies in augmenting therapeutic intervention against HCV.


2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 283-283
Author(s):  
Mariana Álvarez Pérez ◽  
Carolina Robles-Rodriguez ◽  
Laura González Dávalos ◽  
Armando Shimada ◽  
Alfredo Varela ◽  
...  

Abstract During the first and second weeks of life, calves are extremely susceptible to enteric diseases, their digestive tract is developing and their thermoregulation is not adequate; these being some factors that can contribute to the lack of their weight gain (Hulbert & Moisá, 2016). In addition, they have a reduced capacity to generate an innate and adaptive immune response, in other words, they are still not immunocompetent (Costa et al., 2017; Hulbert & Moisá, 2016), since they are born with all the essential immune components but many of them are not functional until calves are at least 2 to 4 weeks old (Chase et al., 2008). With the aim to identify the development of the innate immune response through the expression of MyD88, TRAF6, NFKB1, and NFKB1a mRNA, in different ages and regions of the digestive tract, qPCR tests were held. Twelve Zebu crossbred calves of 0, 7, 28, and 42 days of age were sampled (three animals of each age). Tissue samples included: rumen, duodenum, and ileum. Gene expression was determined by quantitative PCR (qPCR). Changes in the expression of TRAF6, NFKB1 and NFKB1a mRNA were different in rumen and ileum (P &lt; 0.05) at day 28 of age. MYD88 mRNA expression was different only in ileum (P &lt; 0.05). MyD88, TRAF6, NFKB1, and NFKB1a mRNA expression of rumen tended to decrease and in the case of ileum to increase with age; however, this was until day 28 and not in the first week of life, as mentioned by some other authors.


2021 ◽  
Vol 8 ◽  
Author(s):  
Yan-ping Tang ◽  
Yi-xin Yin ◽  
Ming-zhi Xie ◽  
Xin-qiang Liang ◽  
Ji-lin Li ◽  
...  

Background: The role of hyaluronan-mediated motility receptor (HMMR) in colorectal cancer (CRC) remains unclear. The present study aimed to explore the association of HMMR with the development and prognosis of CRC using sequence datasets, clinical tissues, blood samples, and cell lines.Methods: CRC datasets were downloaded from TCGA and GEO databases. Forty CRC tissue samples, 120 CRC blood samples, and 100 healthy controls were collected. Four CRC cell lines (HCT116, HT-29, LoVo, and SW480) and one normal human colon mucosal epithelial cell line (NCM460) were cultured. RT-qPCR was used to determine the expression of HMMR in the tissues and cell lines. ELISA was used to measure HMMR levels in the blood samples.Results: The expression of HMMR was significantly increased in CRC tissues than in corresponding adjacent tissues based on TCGA and GEO datasets, and clinical CRC tissues. No associations were found between the expression of HMMR and the TNM stage or other clinical parameters. The expression of HMMR varied in different CRC cell lines. The blood levels of HMMR tended to be higher in patients with CRC than in healthy controls. TCGA and GEO datasets showed inconsistent results regarding the association of HMMR expression with the survival of patients with CRC.Conclusion: The expression of HMMR is increased in CRC tissues but not in the blood. The expression of HMMR is independent of CRC development and has no prognostic significance in patients with CRC.


2020 ◽  
Vol 94 ◽  
Author(s):  
A. Cruz-Tamayo ◽  
R. González-Garduño ◽  
G. Torres-Hernández ◽  
C. Becerril-Pérez ◽  
O. Hernández-Mendo ◽  
...  

Abstract The objective of this study was to evaluate the reduction in nematode faecal egg count (FEC) in Pelibuey lambs segregated as resistant (RES), susceptible (SUS) and intermediate (INT) to gastrointestinal nematodes. Twenty-nine weaned Pelibuey lambs, aged five months old, free of nematode infection, were used. Nine lambs were RES, six were SUS and 14 were INT lambs. The study consisted of two phases: in Phase 1 the lambs were infected experimentally with Haemonchus contortus. In Phase 2, the lambs were naturally infected by grazing. Faecal and blood samples were taken every week. The packed cell volume and total protein were quantified. The FEC value (FECmax) per lamb was recorded together with a natural reduction in FEC in the two phases. The data were analysed with a model of measures repeated over time. During Phase 1, the RES lambs showed the lowest FEC (1061 ± 1053) compared to the other groups (INT: 2385 ± 1794 eggs per gram of faeces (EPG); and SUS: 3958 ± 3037 EPG). However, in Phase 2 no significant differences (p > 0.05) were observed between the groups of lambs (RES: 275 ± 498 EPG; SUS: 504 ± 1036 EPG; and INT: 603 ± 1061 EPG). At the end of Phase 1, the FEC of RES lambs was naturally reduced by 75.5% in respect to FECmax (p < 0.05), and at the end of Phase 2 the reduction in FEC was 90% in respect to FECmax (p > 0.05); the same behaviour was observed in RES and SUS lambs. It is concluded that the artificial infection in the lambs induced a more rapid immune response in RES than SUS lambs, and all lambs developed high acquired resistance by continuous infection.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mohamed Helmy ◽  
Kumar Selvarajoo

The majority of human genome are non-coding genes. Recent research have revealed that about half of these genome sequences make up of transposable elements (TEs). A branch of these belong to the endogenous retroviruses (ERVs), which are germline viral infection that occurred over millions of years ago. They are generally harmless as evolutionary mutations have made them unable to produce viral agents and are mostly epigenetically silenced. Nevertheless, ERVs are able to express by still unknown mechanisms and recent evidences have shown links between ERVs and major proinflammatory diseases and cancers. The major challenge is to elucidate a detailed mechanistic understanding between them, so that novel therapeutic approaches can be explored. Here, we provide a brief overview of TEs, human ERVs and their links to microbiome, innate immune response, proinflammatory diseases and cancer. Finally, we recommend the employment of systems biology approaches for future HERV research.


mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Alain P. Gobert ◽  
Yvonne L. Latour ◽  
Mohammad Asim ◽  
Jordan L. Finley ◽  
Thomas G. Verriere ◽  
...  

ABSTRACT The reverse transsulfuration pathway is the major route for the metabolism of sulfur-containing amino acids. The role of this metabolic pathway in macrophage response and function is unknown. We show that the enzyme cystathionine γ-lyase (CTH) is induced in macrophages infected with pathogenic bacteria through signaling involving phosphatidylinositol 3-kinase (PI3K)/MTOR and the transcription factor SP1. This results in the synthesis of cystathionine, which facilitates the survival of pathogens within myeloid cells. Our data demonstrate that the expression of CTH leads to defective macrophage activation by (i) dysregulation of polyamine metabolism by depletion of S-adenosylmethionine, resulting in immunosuppressive putrescine accumulation and inhibition of spermidine and spermine synthesis, and (ii) increased histone H3K9, H3K27, and H3K36 di/trimethylation, which is associated with gene expression silencing. Thus, CTH is a pivotal enzyme of the innate immune response that disrupts host defense. The induction of the reverse transsulfuration pathway by bacterial pathogens can be considered an unrecognized mechanism for immune escape. IMPORTANCE Macrophages are professional immune cells that ingest and kill microbes. In this study, we show that different pathogenic bacteria induce the expression of cystathionine γ-lyase (CTH) in macrophages. This enzyme is involved in a metabolic pathway called the reverse transsulfuration pathway, which leads to the production of numerous metabolites, including cystathionine. Phagocytized bacteria use cystathionine to better survive in macrophages. In addition, the induction of CTH results in dysregulation of the metabolism of polyamines, which in turn dampens the proinflammatory response of macrophages. In conclusion, pathogenic bacteria can evade the host immune response by inducing CTH in macrophages.


2015 ◽  
Vol 29 (3) ◽  
pp. 119-129 ◽  
Author(s):  
Richard J. Stevenson ◽  
Deborah Hodgson ◽  
Megan J. Oaten ◽  
Luba Sominsky ◽  
Mehmet Mahmut ◽  
...  

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.


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