scholarly journals In utero heat stress alters the postnatal innate immune response of pigs

2020 ◽  
Vol 98 (12) ◽  
Author(s):  
Jay S Johnson ◽  
Jacob M Maskal ◽  
Alan W Duttlinger ◽  
Kouassi R Kpodo ◽  
Betty R McConn ◽  
...  
Keyword(s):  
Immune Response ◽  
Heat Stress ◽  
Stress Response ◽  
Body Temperature ◽  
Innate Immune Response ◽  
In Utero ◽  
Innate Immune ◽  
Postnatal Life ◽  
Lps Challenge ◽  
Cell Counts

Abstract The effects of in utero heat stress (IUHS) range from decreased growth performance to altered behavior, but the long-term impact of IUHS on postnatal innate immune function in pigs is unknown. Therefore, the study objective was to determine the effects of early gestation IUHS on the immune, metabolic, and stress response of pigs subjected to an 8 hr lipopolysaccharide (LPS) challenge during postnatal life. Twenty-four pregnant gilts were exposed to thermoneutral (TN; n = 12; 17.5 ± 2.1 °C) or heat stress (HS; n = 12; cyclic 26 to 36 °C) conditions from days 6 to 59 of gestation, and then TN conditions (20.9 ± 2.3 °C) from day 60 of gestation to farrowing. At 12 wk of age, 16 IUHS and 16 in utero thermoneutral (IUTN) pigs were selected, balanced by sex and given an intravenous injection of LPS (2 µg/kg BW mixed with sterile saline [SAL] and injected at 2 µL/kg BW) or SAL (2 µL/kg BW). Body temperature was monitored every 30 min, and blood was obtained at 0, 1, 2, 3, 4, 6, and 8 hr following the LPS challenge. Blood samples were analyzed for glucose, insulin, non-esterified fatty acids (NEFA), cortisol, and cytokine concentrations. In addition, white blood cell counts were determined at 0 and 4 hr. Hour 0 data were used as covariates. Body temperature was increased (P < 0.01) in LPS (40.88 ± 0.08 °C) vs. SAL (39.83 ± 0.08 °C) pigs. Eosinophils tended to be decreased overall (P = 0.09; 43.9%) in IUHS vs. IUTN pigs. Glucose concentrations were reduced overall (P = 0.05; 5.9%) in IUHS vs. IUTN pigs. The NEFA concentrations tended to be greater (P = 0.07; 143.4%) in IUHS-LPS pigs compared with all other treatments, and IUTN-LPS pigs tended to have greater (127.4%) circulating NEFA concentrations compared with IUTN-SAL and IUHS-SAL pigs. Cortisol was increased (P = 0.04) in IUHS-LPS compared with IUTN-LPS pigs at 3 hr (21.5%) and 4 hr (64.3%). At 1 hr, tumor necrosis factor α was increased (P = 0.01; 115.1%) in IUHS-LPS compared with IUTN-LPS pigs. Overall, interleukin-1β (IL-1β) and interleukin-6 (IL-6) were greater (P < 0.04; 281.3% and 297.8%, respectively) in IUHS-LPS pigs compared with all other treatments, and IUTN-LPS pigs had increased IL-1β and IL-6 concentrations compared with IUTN-SAL and IUHS-SAL pigs. In summary, IUHS altered the postnatal cytokine, metabolic, and physiological stress response of pigs during postnatal life, which may have negative implications toward the innate immune response of IUHS pigs to pathogens.

scholarly journals 234 In utero heat stress alters the postnatal immune and metabolic response of growing pigs subjected to a lipopolysaccharide challenge

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 116-116
Author(s):  
Jay S Johnson ◽  
Jacob M Maskal ◽  
Alan W Duttlinger ◽  
Kouassi R Kpodo ◽  
Betty R McConn ◽  
...  
Keyword(s):  
Heat Stress ◽  
Body Temperature ◽  
Metabolic Response ◽  
In Utero ◽  
Growing Pigs ◽  
Postnatal Life ◽  
Study Objective ◽  
Lps Challenge ◽  
Long Term Impact

Abstract In utero heat stress (IUHS) reduces swine productivity and welfare but little is known about the long-term impact on immune function. The study objective was to determine the effects of IUHS on the immune and metabolic response of pigs subjected to an 8 h lipopolysaccharide (LPS) challenge during postnatal life. Twenty-four pregnant gilts were exposed to thermoneutral (TN; n = 12; 17.5 ± 2.1⁰C) or heat stress (HS; n = 12; cyclical 27°C-37°C) conditions from d 1 to 58 of gestation, and TN conditions from d 59 of gestation to farrowing. After farrowing, all piglets were housed under the same conditions. At 12 weeks post-farrowing, 16 IUHS and 16 in utero thermoneutral (IUTN) pigs were selected, balanced by sex and given an intravenous injection of LPS (2 µg/kg BW) or saline (SAL). Treatment combinations were: IUTN-SAL, IUTN-LPS, IUHS-SAL, IUHS-LPS. Body temperature was monitored in 30-min intervals and blood samples were obtained at 0, 1, 2, 3, 4, 6, and 8 h. Blood was analyzed for glucose, insulin, non-esterified fatty acids (NEFA), and cytokine concentrations. Body temperature increased (P < 0.01; 1.05°C) in LPS versus SAL pigs, regardless of in utero treatment. Glucose concentrations were reduced overall (P = 0.05; 5.9%) in IUHS versus IUTN pigs. Non-esterified fatty acid concentrations tended to be greater (P = 0.07; 143.4%) in IUHS-LPS pigs compared to all other treatments, and IUTN-LPS pigs tended to have greater circulating NEFA concentrations (127.4%) compared to IUTN-SAL and IUHS-SAL pigs. At 1 h, TNFα was increased (P = 0.01; 115.1%) in IUHS-LPS compared to IUTN-LPS pigs. Overall, IL-1β and IL-6 were greater (P < 0.04; 56.0 and 46.8%, respectively) in IUHS-LPS compared IUTN-LPS pigs. In summary, IUHS altered the postnatal immune and metabolic response of pigs during postnatal life, which has negative implications towards future disease susceptibility.

scholarly journals The hepatic innate immune response is lobe-specific in a murine model endotoxemia

2019 ◽  
Vol 25 (2) ◽  
pp. 144-154 ◽  
Author(s):  
Leanna Nguyen ◽  
Jeryl Sandoval ◽  
Robyn De Dios ◽  
Elesa Yihdego ◽  
Miguel Zarate ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Innate Immune Response ◽  
Early Time ◽  
Innate Immune ◽  
Immune Response Gene ◽  
Hepatic Tissue ◽  
Transcriptional Responses ◽  
Time Points ◽  
Lps Challenge

The liver plays a central role in the innate immune response to endotoxemia. While previous studies have demonstrated lobe-specific transcriptional responses to various insults, whether this is true in response to endotoxemia is unknown. We sought to assess whether there were significant intra- and inter-lobe differences in the murine hepatic innate immune transcriptional response to endotoxemia. Adult male ICR mice were exposed to i.p. LPS (5 mg/kg, 30 min, 60 min, 5 h) and primary ( Tnf, Cxcl1, Nfkbia, Tnfiap3) and secondary ( Il6, Nos2) innate immune response gene expression was assessed in the left medial, right medial, left lateral, and right lateral lobes, and the papillary and caudate processes. The expression of all innate immune response genes increased following i.p. LPS challenge. When tested at the early time points (30 and 60 min), the left medial lobe and caudate process consistently demonstrated the highest induction of gene expression. Most inter-lobe differences were attenuated at later time points (5 h). To improve reproducibility of the study of endotoxemia induced by i.p. LPS challenge, inclusion of appropriate methodological details regarding collection of hepatic tissue should be included when reporting scientific results in published manuscripts.

scholarly journals Analysis of the basal colonic innate immune response of pigs divergent in feed efficiency and following an ex vivo lipopolysaccharide challenge

2019 ◽  
Vol 51 (9) ◽  
pp. 443-448 ◽  
Author(s):  
Stafford Vigors ◽  
John V. O’ Doherty ◽  
Marion Ryan ◽  
Torres Sweeney
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Feed Efficiency ◽  
Ex Vivo ◽  
Innate Immune ◽  
Colonic Tissue ◽  
Experimental Conditions ◽  
Defense Proteins ◽  
Lps Challenge ◽  
Genes Encoding

While feed efficiency is influenced by multiple physiological processes, it is not known how efficient and inefficient pigs differ in relation to their basal immune response, and particularly their innate immune response to a microbial challenge. Hence, the objective was to examine the expression of genes encoding innate immune response markers in basal colonic tissue and colonic tissue following an ex vivo lipopolysaccharide (LPS) challenge from pigs divergent in residual feed intake (RFI). Pigs that differed in RFI were selected from two different farms of origin. Colonic tissue was harvested from high RFI (HRFI) and low (LRFI) pigs, and two experimental conditions were explored: the first was basal unchallenged tissue and the second was colonic tissue following an ex vivo LPS challenge. RNA was extracted and tested on a Nanostring panel of 72 genes coding for barrier defense proteins, transmembrane receptors, kinases, transcription regulators, cytokines, and cytokine regulators. In the basal unchallenged tissue, the LRFI pigs had increased expression of AOAH, AP1, and TRAM and the cytokines TNF, IL10, and CXCL8, compared with the HRFI pigs ( P < 0.05), with a significant effect of farm of origin on 31 genes ( P < 0.05). In the LPS-challenged tissues, the LRFI group had higher expression of TLR1, TLR7, TLR8, GPR43/FFAR2, JAK2, and NFAM1 compared with the HRFI group ( P < 0.05). In conclusion, these data suggest that LRFI pigs have an upregulated basal colonic inflammatory state and a heightened response to an LPS challenge compared with the inefficient HRFI pigs. This immune profile potentially enhances their capacity to respond to an infectious challenge.

scholarly journals Induction of an Embryonic Mouse Innate Immune Response following Inoculation In Utero with Minute Virus of Mice

2014 ◽  
Vol 89 (4) ◽  
pp. 2182-2191 ◽  
Author(s):  
Irina Rostovsky ◽  
Claytus Davis
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
In Utero ◽  
Innate Immune ◽  
Productive Infection ◽  
Interferon Response ◽  
Minute Virus Of Mice ◽  
Embryonic Mouse ◽  
Minute Virus ◽  
Ifn Γ

ABSTRACTWe used an embryonic-infection model system to show that MVMp, the prototypic minute virus of mice (MVM) serotype and a member of the genusProtoparvovirus, triggers a comprehensive innate immune response in the developing mouse embryo. Direct inoculation of the midtrimester embryoin uterowith MVMp results in a widespread, productive infection. During a 96-h infection course, embryonic beta interferon (IFN-β) and IFN-γ transcription were induced 90- and 60-fold, respectively. IFN-β levels correlated with the embryo viral burden, while IFN-γ levels first increased and then decreased. Production of proinflammatory cytokines, interleukin 1β (IL-1β) and tumor necrosis factor alpha (TNF-α), also increased, but by smaller amounts, approximately 7-fold each. We observed increased levels of downstream antiviral effector molecules, PKR and phosphorylated STAT2. Finally, we showed that there is an immune cell response to the virus infection. Infected tissues in the embryo exhibited an increased density of mature leukocytes compared to the same tissues in uninfected embryos. The responses we observed were almost completely restricted to the infected embryos. Uninfected littermates routinely exhibited small increases in innate immune components that rarely reached statistical significance compared to negative controls. Similarly, the placentae of infected embryos did not show any significant increase in transcription of innate immune cytokines. Since the placenta has both embryonic and maternal components, we suggest there is minimal involvement of the dam in the response to infection.IMPORTANCEInteraction between the small single-stranded vertebrate DNA viruses, the protoparvoviruses, and the host innate immune system has been unclear. The issue is important practically given the potential use of these viruses as oncotherapeutic agents. The data reported here stand in contrast to studies of innate immune response during protoparvovirus infection of adult hosts, which invariably reported no or minimal and sporadic induction of an interferon response during infection. We conclude that under conditions of robust and productive MVM infection, a normal murine host is able to mount a significant and broad innate immune response.

scholarly journals SPOP Promotes Ubiquitination and Degradation of MyD88 to Suppress the Innate Immune Response

2019 ◽  
Author(s):  
Qinghe Li ◽  
Fei Wang ◽  
Qiao Wang ◽  
Maiqing Zheng ◽  
Ranran Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
Autoimmune Diseases ◽  
Salmonella Typhimurium ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Negative Regulator ◽  
Microbial Pathogens ◽  
Genetic Ablation ◽  
Susceptibility To Infection ◽  
Lps Challenge

AbstractAs a canonical adaptor for Toll-like receptor (TLR) family, MyD88 has crucial roles in host defence against infection of microbial pathogens and its dysregulation might induce autoimmune diseases. Here we demonstrate that the Cullin 3-based ubiquitin ligase adaptor SPOP recognizes the intermediate domain and degrades chMyD88 through the proteasome pathway. Knockdown or genetic ablation of chSPOP leads to aberrant elevation of the chMyD88 protein. Consequently, ChSPOP negatively regulates the activity of NF-κB pathway and thus the production of IL-1β and IL-8 upon LPS challenge. Furthermore, SPOP deficiency mice are more susceptible to infection of Salmonella typhimurium. Collectively, these findings demonstrate chMyD88 as a bona fide substrate of chSPOP and uncover a mechanism by which chSPOP suppresses the innate immune signaling.Author SummaryMyD88 is a central adaptor mediating the initiate of innate immune response and production of proinflammatory cytokines that restrain pathogens and activate adaptive immunity. Although MyD88 is crucial for the host to prevent pathogenic infection, misregulation of MyD88 abundance might lead to autoimmune diseases. Thus, degradation of MyD88 is a canonical mechanism to terminate cytokines production. Here we characterized a novel E3 ligase SPOP that target MyD88 for degradation. SPOP attenuated IL1β and IL8 production through K48-linked polyubiquitination and degradation of MyD88 and thus impaired immune responses. SPOP deficient mice show more susceptibility to infection by Salmonella typhimurium. These findings demonstrate that SPOP is a negative regulator of MyD88-dependent pathway activation triggered by LPS and Salmonella typhimurium, which helps the host to maintain immune homeostasis.

scholarly journals Murine Norovirus infection results in anti-inflammatory response downstream of amino acids depletion in macrophages

2021 ◽  
Author(s):  
Michèle Brocard ◽  
Jia Lu ◽  
Belinda Hall ◽  
Khushboo Borah ◽  
Carla Moller-Levet ◽  
...  
Keyword(s):  
Immune Response ◽  
Amino Acid ◽  
Stress Response ◽  
Viral Infection ◽  
Innate Immune Response ◽  
Metabolic Stress ◽  
Innate Immune ◽  
Murine Norovirus ◽  
Anti Inflammatory ◽  
Inflammatory Signalling

AbstractMurine norovirus (MNV) infection results in a late translation shut-off, that is proposed to contribute to the attenuated and delayed innate immune response observed both in vitro and in vivo. Recently, we further demonstrated the activation of the eIF2α kinase GCN2 during MNV infection, which has been previously linked to immunomodulation and resistance to inflammatory signalling during metabolic stress. While viral infection is usually associated with activation of dsRNA binding pattern recognition receptor PKR, we hypothesised that the establishment of a metabolic stress in infected cells is a proviral event, exploited by MNV to promote replication through weakening the activation of the innate immune response. In this study, we used multi-omics approaches to characterise cellular responses during MNV replication. We demonstrate the activation of pathways related to the integrated stress response, a known driver of anti-inflammatory phenotypes in macrophages. In particular, MNV infection causes an amino acid imbalance that is associated with GCN2 and ATF2 signalling. Importantly, this reprogramming lacks the features of a typical innate immune response, with the ATF/CHOP target GDF15 contributing to the lack of antiviral responses. We propose that MNV-induced metabolic stress supports the establishment of host tolerance to viral replication and propagation.ImportanceDuring viral infection, host defences are typically characterised by the secretion of pro-inflammatory autocrine and paracrine cytokines, potentiation of the IFN response and induction of the anti-viral response via activation of JAK and Stat signalling. To avoid these and propagate viruses have evolved strategies to evade or counteract host sensing. In this study, we demonstrate that murine norovirus controls the antiviral response by activating a metabolic stress response that activates the amino acid response and impairs inflammatory signalling. This highlights novel tools in the viral countermeasures tool-kit, and demonstrates the importance of the currently poorly understood metabolic reprogramming occurring during viral infections.

Evaluation of breed-dependent differences in the innate immune responses of Holstein and Jersey cows toStaphylococcus aureusintramammary infection

2008 ◽  
Vol 75 (3) ◽  
pp. 291-301 ◽  
Author(s):  
Douglas D Bannerman ◽  
Hayley R Springer ◽  
Max J Paape ◽  
Adam CW Kauf ◽  
Jesse P Goff
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Phenotypic Traits ◽  
Related Factors ◽  
Intramammary Infection ◽  
Amyloid A ◽  
Cell Counts ◽  
Tumour Growth Factor ◽  
Jersey Cows

Mastitis is one of the most prevalent diseases of cattle. Various studies have reported breed-dependent differences in the risk for developing this disease. Among two major breeds, Jersey cows have been identified as having a lower prevalence of mastitis than Holstein cows. It is well established that the nature of the initial innate immune response to infection influences the ability of the host to clear harmful bacterial pathogens. Whether differences in the innate immune response to intramammary infections explain, in part, the differential prevalence of mastitis in Holstein and Jersey cows remains unknown. The objective of the current study was to evaluate several parameters of the innate immune response of Holstein and Jersey cows to intramammary infection withStaphylococcus aureus, a common mastitis-inducing pathogen. To control for non-breed related factors that could influence these parameters, all cows were of the same parity, in similar stages of milk production, housed and managed under identical conditions, and experimentally infected and sampled in parallel. The following parameters of the innate immune response were evaluated: acute phase protein synthesis of serum amyloid A and lipopolysaccharide-binding protein; total and differential circulating white blood cell counts; milk somatic cell counts; mammary vascular permeability; milk N-acetyl-beta-d-glucosaminidase (NAGase) activity; and production of the cytokines, interferon (IFN)-γ, interleukin (IL)-12, tumour growth factor(TGF)-α, and TGF-β1. The temporal response of all of these parameters following infection was similar between Holstein and Jersey cows. Further, with the exception of changes in circulating neutrophils and NAGase activity, the overall magnitude of these parameters were also comparable. Together, these data demonstrate that the innate immune response of Holstein and Jersey cows toStaph. aureusintramammary infection remains highly conserved despite previously reported differences in mastitis prevalence, as well as genotypic and phenotypic traits, that exist between the two breeds.

scholarly journals Murine Norovirus infection results in anti-inflammatory response downstream of amino acid depletion in macrophages.

2021 ◽  
Author(s):  
Michèle Brocard ◽  
Jia Lu ◽  
Belinda Hall ◽  
Khushboo Borah ◽  
Carla Moller-Levet ◽  
...  
Keyword(s):  
Immune Response ◽  
Amino Acid ◽  
Stress Response ◽  
Viral Infection ◽  
Innate Immune Response ◽  
Metabolic Stress ◽  
Innate Immune ◽  
Murine Norovirus ◽  
Anti Inflammatory ◽  
Inflammatory Signalling

Murine norovirus (MNV) infection results in a late translation shut-off, that is proposed to contribute to the attenuated and delayed innate immune response observed both in vitro and in vivo. Recently, we further demonstrated the activation of the eIF2α kinase GCN2 during MNV infection, which has been previously linked to immunomodulation and resistance to inflammatory signalling during metabolic stress. While viral infection is usually associated with activation of dsRNA binding pattern recognition receptor PKR, we hypothesised that the establishment of a metabolic stress in infected cells is a proviral event, exploited by MNV to promote replication through weakening the activation of the innate immune response. In this study, we used multi-omics approaches to characterise cellular responses during MNV replication. We demonstrate the activation of pathways related to the integrated stress response, a known driver of anti-inflammatory phenotypes in macrophages. In particular, MNV infection causes an amino acid imbalance that is associated with GCN2 and ATF2 signalling. Importantly, this reprogramming lacks the features of a typical innate immune response, with the ATF/CHOP target GDF15 contributing to the lack of antiviral responses. We propose that MNV-induced metabolic stress supports the establishment of host tolerance to viral replication and propagation. Importance During viral infection, host defences are typically characterised by the secretion of pro-inflammatory autocrine and paracrine cytokines, potentiation of the IFN response and induction of the anti-viral response via activation of JAK and Stat signalling. To avoid these and propagate viruses have evolved strategies to evade or counteract host sensing. In this study, we demonstrate that murine norovirus controls the antiviral response by activating a metabolic stress response that activates the amino acid response and impairs inflammatory signalling. This highlights novel tools in the viral countermeasures arsenal, and demonstrates the importance of the currently poorly understood metabolic reprogramming occurring during viral infections.

Lactobacillus casei: influence on the innate immune response and haemostatic alterations in a liver-injury model

2009 ◽  
Vol 55 (6) ◽  
pp. 648-656 ◽  
Author(s):  
Cecilia Haro ◽  
Hortensia Zelaya ◽  
Sandra Lazarte ◽  
Susana Alvarez ◽  
Graciela Agüero
Keyword(s):  
Immune Response ◽  
Liver Injury ◽  
Innate Immune Response ◽  
Preventive Treatment ◽  
Innate Immune ◽  
Myeloperoxidase Activity ◽  
Blood Leukocytes ◽  
Cell Counts ◽  
White Blood Cell Counts ◽  
Serum Aminotransferases

Lactobacilllus casei CRL 431 has the ability to modulate the local and systemic immune responses, which are significantly involved in liver injury caused by hepatotoxins. This work was conducted to determine whether L. casei has a preventive effect on the hepatic damage undergone during an acute liver injury (ALI). Methods: ALI was induced by an intraperitoneal injection of d-galactosamine (D-Gal). Different groups of mice received 1× 109 L. casei cells/day/mouse for 2 days before D-Gal injection. Blood and liver samples were obtained 0, 6, 12, and 24 h after D-Gal administration. Results: D-Gal induced increases in serum aminotransferases, reduced the number of blood leukocytes, enhanced neutrophil myeloperoxidase activity, increased dead cells, and altered prothrombin time and plasma fibrinogen levels. The preventive treatment with L. casei for 2 days modulated the innate immune response. This effect was shown by the earlier normalization of white blood cell counts, myeloperoxidase activity and aminotransferases levels. However, the haemostatic parameters were only partially recovered. The favourable effects obtained could be due to the capacity of L. casei to moderate the inflammatory response at the site of the injury with less damage to liver tissue.

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