scholarly journals Experimental Fasciola hepatica Infection Alters Responses to Tests Used for Diagnosis of Bovine Tuberculosis

2006 ◽  
Vol 75 (3) ◽  
pp. 1373-1381 ◽  
Author(s):  
Robin J. Flynn ◽  
Celine Mannion ◽  
Olwen Golden ◽  
Orcun Hacariz ◽  
Grace Mulcahy
Keyword(s):  
Immune Responses ◽  
Bovine Tuberculosis ◽  
Helminth Infection ◽  
Fasciola Hepatica ◽  
Correct Diagnosis ◽  
Interleukin 4 ◽  
Bacterial Disease ◽  
Predictive Capacity ◽  
The Impact

ABSTRACT Fasciola hepatica is a prevalent helminth parasite of livestock. Infection results in polarization of the host's immune response and generation of type 2 helper (Th2) immune responses, which are known to be inhibitory to Th1 responses. Bovine tuberculosis (BTB) is a bacterial disease of economic and zoonotic importance. Control polices for this disease rely on extensive annual testing and a test-and-slaughter policy. The correct diagnosis of BTB relies on cell-mediated immune responses. We established a model of coinfection of F. hepatica and Mycobacterium bovis BCG to examine the impact of helminth infection on correct diagnosis. We found the predictive capacity of tests to be compromised in coinfected animals and that F. hepatica infection altered macrophage function. Interleukin-4 and gamma interferon expression in whole-blood lymphocytes restimulated in vitro with M. bovis antigen was also altered in coinfected animals. These results raise the question of whether F. hepatica infection can affect the predictive capacity of tests for the diagnosis of BTB and possibly also influence susceptibility to BTB and other bacterial diseases. Further studies on the interplay between helminth infection and BTB are warranted.

scholarly journals Reduced Protective Efficacy of a Blood-Stage Malaria Vaccine by Concurrent Nematode Infection

2006 ◽  
Vol 74 (4) ◽  
pp. 2138-2144 ◽  
Author(s):  
Zhong Su ◽  
Mariela Segura ◽  
Mary M. Stevenson
Keyword(s):  
Immune Responses ◽  
Malaria Vaccine ◽  
Transforming Growth Factor ◽  
Protective Efficacy ◽  
Nematode Infection ◽  
Blood Stage ◽  
Interleukin 4 ◽  
Spleen Cells ◽  
The Impact

ABSTRACT Helminth infections, which are prevalent in areas where malaria is endemic, have been shown to modulate immune responses to unrelated pathogens and have been implicated in poor efficacy of malaria vaccines in humans. We established a murine coinfection model involving blood-stage Plasmodium chabaudi AS malaria and a gastrointestinal nematode, Heligmosomoides polygyrus, to investigate the impact of nematode infection on the protective efficacy of a malaria vaccine. C57BL/6 mice immunized with crude blood-stage P. chabaudi AS antigen in TiterMax adjuvant developed strong protection against malaria challenge. The same immunization protocol failed to induce strong protection in H. polygyrus-infected mice. Immunized nematode-infected mice produced significantly lower levels of malaria-specific antibody than nematode-free mice produced. In response to nematode and malarial antigens, spleen cells from immunized nematode-infected mice produced significantly lower levels of gamma interferon but more interleukin-4 (IL-4), IL-13, and IL-10 in vitro than spleen cells from immunized nematode-free mice produced. Furthermore, H. polygyrus infection also induced a strong transforming growth factor β1 response in vivo and in vitro. Deworming treatment of H. polygyrus-infected mice before antimalarial immunization, but not deworming treatment after antimalarial immunization, restored the protective immunity to malaria challenge. These results demonstrate that concurrent nematode infection strongly modulates immune responses induced by an experimental malaria vaccine and consequently suppresses the protective efficacy of the vaccine against malaria challenge.

scholarly journals Oxidative Stress Compromises Lymphocyte Function in Neonatal Dairy Calves

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 255
Author(s):  
Wilmer Cuervo ◽  
Lorraine M. Sordillo ◽  
Angel Abuelo
Keyword(s):  
Oxidative Stress ◽  
Immune Responses ◽  
Immune Cell ◽  
Lymphocyte Activation ◽  
Dairy Calves ◽  
Lymphocyte Function ◽  
Newborn Calves ◽  
Ifn Γ ◽  
The Impact

Dairy calves are unable to mount an effective immune response during their first weeks of life, which contributes to increased disease susceptibility during this period. Oxidative stress (OS) diminishes the immune cell capabilities of humans and adult cows, and dairy calves also experience OS during their first month of life. However, the impact that OS may have on neonatal calf immunity remains unexplored. Thus, we aimed to evaluate the impact of OS on newborn calf lymphocyte functions. For this, we conducted two experiments. First, we assessed the association of OS status throughout the first month of age and the circulating concentrations of the cytokines interferon-gamma (IFN-γ) and interleukin (IL) 4, as well as the expression of cytokine-encoding genes IFNG, IL2, IL4, and IL10 in peripheral mononuclear blood cells (PBMCs) of 12 calves. Subsequently, we isolated PBMCs from another 6 neonatal calves to investigate in vitro the effect of OS on immune responses in terms of activation of lymphocytes, cytokine expression, and antibody production following stimulation with phorbol 12-myristate 13-acetate or bovine herpesvirus-1. The results were compared statistically through mixed models. Calves exposed to high OS status in their first month of age showed higher concentrations of IL-4 and expression of IL4 and IL10 and lower concentrations of IFN-γ and expression of IFNG and IL2 than calves exposed to lower OS. In vitro, OS reduced lymphocyte activation, production of antibodies, and protein and gene expression of key cytokines. Collectively, our results demonstrate that OS can compromise some immune responses of newborn calves. Hence, further studies are needed to explore the mechanisms of how OS affects the different lymphocyte subsets and the potential of ameliorating OS in newborn calves as a strategy to augment the functional capacity of calf immune cells, as well as enhance calves’ resistance to infections.

scholarly journals Interleukin 4 Moderately Affects Competence of Pluripotent Stem Cells for Myogenic Conversion

2019 ◽  
Vol 20 (16) ◽  
pp. 3932 ◽  
Author(s):  
Barbara Świerczek-Lasek ◽  
Jacek Neska ◽  
Agata Kominek ◽  
Łukasz Tolak ◽  
Tomasz Czajkowski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Pluripotent Stem Cells ◽  
Muscle Development ◽  
Embryonic Stem ◽  
Interleukin 4 ◽  
Myogenic Cells ◽  
The Impact

Pluripotent stem cells convert into skeletal muscle tissue during teratoma formation or chimeric animal development. Thus, they are characterized by naive myogenic potential. Numerous attempts have been made to develop protocols enabling efficient and safe conversion of pluripotent stem cells into functional myogenic cells in vitro. Despite significant progress in the field, generation of myogenic cells from pluripotent stem cells is still challenging—i.e., currently available methods require genetic modifications, animal-derived reagents, or are long lasting—and, therefore, should be further improved. In the current study, we investigated the influence of interleukin 4, a factor regulating inter alia migration and fusion of myogenic cells and necessary for proper skeletal muscle development and maintenance, on pluripotent stem cells. We assessed the impact of interleukin 4 on proliferation, selected gene expression, and ability to fuse in case of both undifferentiated and differentiating mouse embryonic stem cells. Our results revealed that interleukin 4 slightly improves fusion of pluripotent stem cells with myoblasts leading to the formation of hybrid myotubes. Moreover, it increases the level of early myogenic genes such as Mesogenin1, Pax3, and Pax7 in differentiating embryonic stem cells. Thus, interleukin 4 moderately enhances competence of mouse pluripotent stem cells for myogenic conversion.

scholarly journals Bartonella henselae-Specific Cell-Mediated Immune Responses Display a Predominantly Th1 Phenotype in Experimentally Infected C57BL/6 Mice

2001 ◽  
Vol 69 (10) ◽  
pp. 6427-6433 ◽  
Author(s):  
Mardjan Arvand ◽  
Ralf Ignatius ◽  
Thomas Regnath ◽  
Helmut Hahn ◽  
Martin E. A. Mielke
Keyword(s):  
Immune Responses ◽  
Bartonella Henselae ◽  
Interleukin 4 ◽  
Infection Model ◽  
Antibody Concentration ◽  
Specific Cell ◽  
Spleen Cells ◽  
Viable Bacteria ◽  
Igg Isotypes

ABSTRACT Immune responses of the immunocompetent host to Bartonella henselae infection were investigated in the murine infection model using C57BL/6 mice. Following intraperitoneal infection with human-derived B. henselae strain Berlin-1, viable bacteria could be recovered from livers and spleens during the first week postinfection, while Bartonella DNA remained detectable by PCR in the liver for up to 12 weeks after infection. Granulomatous lesions developed in livers of infected mice, reached maximal density at 12 weeks after infection, and persisted for up to 20 weeks, indicating that B. henselae induced a chronic granulomatous hepatitis in the immunocompetent murine host. T-cell-mediated immune responses were analyzed in vitro by means of spleen cell proliferation and cytokine release assays as well as analysis of immunoglobulin G (IgG) isotypes. Spleen cells from infected mice proliferated specifically upon stimulation with heat-killedBartonella antigen. Proliferative responses were mainly mediated by CD4+ T cells, increased during the course of infection, peaked at 8 weeks postinfection, and decreased thereafter. Gamma interferon, but not interleukin-4, was produced in vitro by spleen cells from infected animals upon stimulation withBartonella antigens. Bartonella-specific IgG was detectable in serum of infected mice by 2 weeks, and the antibody concentration peaked at 12 weeks postinfection. IgG2b was the prominent isotype among the Bartonella-specific serum IgG antibodies. These data indicate that B. henselaeinduces cell-mediated immune responses with a Th1 phenotype in immunocompetent C57BL/6 mice.

scholarly journals Cryptococcus gattii Infection Dampens Th1 and Th17 Responses by Attenuating Dendritic Cell Function and Pulmonary Chemokine Expression in the Immunocompetent Hosts

2014 ◽  
Vol 82 (9) ◽  
pp. 3880-3890 ◽  
Author(s):  
Pornpimon Angkasekwinai ◽  
Nuntarat Sringkarin ◽  
Oratai Supasorn ◽  
Madtika Fungkrajai ◽  
Yui-Hsi Wang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cell Function ◽  
Cryptococcus Gattii ◽  
Cell Immune Response ◽  
Content Type ◽  
Chemokine Expression ◽  
Immunocompromised Hosts ◽  
The Impact ◽  
Highly Virulent

ABSTRACTCryptococcal infections are primarily caused by two related fungal species:Cryptococcus neoformansandCryptococcus gattii. It is well known thatC. neoformansgenerally affects immunocompromised hosts; however,C. gattiiinfection can cause diseases in not only immunocompromised hosts but also immunocompetent individuals. While recent studies suggest thatC. gattiiinfection could dampen pulmonary neutrophil recruitment and inflammatory cytokine production in immunocompetent hosts, the impact ofC. gattiiinfection on the development of their adaptive T helper cell immune response has not been addressed. Here, we report thatC. neoformansinfection with highly virulent and less virulent strains preferentially induced pulmonary Th1 and Th17 immune responses in the host, respectively. However, fewer pulmonary Th1 and Th17 cells could be detected in mice infected withC. gattiistrains. Notably, dendritic cells (DC) in mice infected withC. gattiiexpressed much lower levels of surface MHC-II andIl12orIl23transcripts and failed to induce effective Th1 and Th17 differentiationin vitro. Furthermore, the expression levels ofIp10andCxcl9transcripts, encoding Th1-attracting chemokines, were significantly reduced in the lungs of mice infected with the highly virulentC. gattiistrain. Thus, our data suggest thatC. gattiiinfection dampens the DC-mediated effective Th1/Th17 immune responses and downregulates the pulmonary chemokine expression, thus resulting in the inability to mount protective immunity in immunocompetent hosts.

scholarly journals Macrophage Activation and Functions during Helminth Infection: Recent Advances from the Laboratory Mouse

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Marion Rolot ◽  
Benjamin G. Dewals
Keyword(s):  
Immune Responses ◽  
Helminth Infection ◽  
Laboratory Mouse ◽  
Alternative Activation ◽  
Recent Advances ◽  
Helminth Infections ◽  
Classically Activated Macrophages

Macrophages are highly plastic innate immune cells that adopt an important diversity of phenotypes in response to environmental cues. Helminth infections induce strong type 2 cell-mediated immune responses, characterized among other things by production of high levels of interleukin- (IL-) 4 and IL-13. Alternative activation of macrophages by IL-4 in vitro was described as an opposite phenotype of classically activated macrophages, but the in vivo reality is much more complex. Their exact activation state as well as the role of these cells and associated molecules in type 2 immune responses remains to be fully understood. We can take advantage of a variety of helminth models available, each of which have their own feature including life cycle, site of infection, or pathological mechanisms influencing macrophage biology. Here, we reviewed the recent advances from the laboratory mouse about macrophage origin, polarization, activation, and effector functions during parasitic helminth infection.

Treatment with synthetic lipophilic tyrosyl ester controls Leishmania major infection by reducing parasite load in BALB/c mice

Parasitology ◽  
2016 ◽  
Vol 143 (12) ◽  
pp. 1615-1621 ◽  
Author(s):  
RABIAA M. SGHAIER ◽  
IMEN AISSA ◽  
HANÈNE ATTIA ◽  
AYMEN BALI ◽  
PABLO A. LEON MARTINEZ ◽  
...  
Keyword(s):  
Immune Responses ◽  
Leishmania Major ◽  
Parasite Load ◽  
Parasite Clearance ◽  
Potential Effect ◽  
Interleukin 4 ◽  
Drug Candidate ◽  
Cytokine Balance

SUMMARYSynthesized lipophilic tyrosyl ester derivatives with increasing lipophilicity were effective against Leishmania (L.) major and Leishmania infantum species in vitro. These findings prompted us to test in vivo leishmanicidal properties of these molecules and their potential effect on the modulation of immune responses. The experimental BALB/c model of cutaneous leishmaniasis was used in this study. Mice were infected with L. major parasites and treated with three in vitro active tyrosyl esters derivatives.Among these tested tyrosylcaprate (TyC) compounds, only TyC10 exhibited an in vivo anti-leishmanial activity, when injected sub-cutaneously (s.c.). TyC10 treatment of L. major-infected BALB/c mice resulted in a decrease of lesion development and parasite load. TyC10 s.c. treatment of non-infected mice induced an imbalance in interferon γ/interleukin 4 (IFN-γ/IL-4) ratio cytokines towards a Th1 response. Our results indicate that TyC10 s.c. treatment improves lesions’ healing and parasite clearance and may act on the cytokine balance towards a Th1 protective response by decreasing IL-4 and increasing IFN-γ transcripts. TyC10 is worthy of further investigation to uncover its mechanism of action that could lead to consider this molecule as a potential drug candidate.

scholarly journals Mechanisms Involved in Type II Macrophage Activation and Effector Functions

2021 ◽  
Author(s):  
◽  
Marie Clare Lydia Kharkrang
Keyword(s):  
Immune Responses ◽  
Inflammatory Responses ◽  
Surface Marker ◽  
Alternative Activation ◽  
Type Ii ◽  
Activated Macrophages ◽  
Phenotypic Properties ◽  
Anti Inflammatory ◽  
The Impact

<p>Autoimmunities are extremely difficult to treat and involved in their pathogenesis are pro-inflammatory immune responses redirected against one's own tissues. Studies in our lab have shown macrophages that are induced to become type II macrophages protect against an animal model of MS, experimental autoimmune encephalomyelitis (EAE), with protection due to immune deviation. Another way to deviate immune responses away from inflammation is by infection with the parasitic helminth Schistosoma mansoni, which also protects against EAE. The contribution of type II macrophages in this protection is unknown, as are the mechanisms involved in promoting the phenotype induced by type II activation. This project investigates key mechanisms involved in type II activation, while also elucidating the possible effect of schistosome exposure on the induction of this activation state. Using a validated model of type II activation in vitro, we compared the effects of schistosome immune complexes on various macrophage properties such as cytokine, surface marker and enzymatic profiles. This thesis identified that exposure to schistosome complexes induces a macrophage state with characteristics of two distinct activation states (type II and alternative activation), as well as completely novel characteristics. This activation state shows many phenotypic properties associated with immune regulation, and may have important consequences for understanding mechanisms involved in protection against inflammatory illnesses. We also investigated key mechanisms involved in the anti-inflammatory responses induced by type II activation. Cytokine, chemokine and surface marker profiles of macrophages were assessed in response to type II activation in vitro, with the main emphasis on determining the effects of IL-10 and CD40 on the type II activation phenotype and function. This investigation found that type II activated macrophages depend on low levels of CD40/CD40L signalling to polarise Th2 development, as the expression of receptors for Th2-inducing cytokines are significantly impaired in the absence of this interaction. This suggests an important role for the low but maintained levels of CD40 on type II activated macrophages, in aiding the deviation of immune responses, while maintaining Th2 polarization. We also suggest a suppressive role of CD40/CD40L in IL-10 production, which is a novel find. The requirement of new treatments for MS is escalating as more people are affected each year. The impact of MS on the quality of life is severe and long lasting. Having a greater understanding of the mechanisms involved in deviating pro-inflammatory or anti-inflammatory responses will enable the development of much more effective treatments and therapies in the future.</p>

scholarly journals RNA interference dynamics in juvenile Fasciola hepatica are altered during in vitro growth and development

2020 ◽  
Author(s):  
Paul McCusker ◽  
Wasim Hussain ◽  
Paul McVeigh ◽  
Erin McCammick ◽  
Nathan G. Clarke ◽  
...  
Keyword(s):  
Rna Interference ◽  
Functional Genomics ◽  
Liver Fluke ◽  
Fasciola Hepatica ◽  
Life Stage ◽  
Life Stages ◽  
Functional Studies ◽  
Rnai Efficiency ◽  
The Impact

AbstractFor over a decade RNA interference (RNAi) has been an important molecular tool for functional genomics studies in parasitic flatworms. Despite this, our understanding of RNAi dynamics in many flatworm parasites, such as the temperate liver fluke (Fasciola hepatica), remains rudimentary. The ability to maintain developing juvenile fluke in vitro provides the opportunity to perform functional studies during development of the key pathogenic life stage. Here, we investigate the RNAi competence of developing juvenile liver fluke. Firstly, all life stages examined possess, and express, core candidate RNAi effectors encouraging the hypothesis that all life stages of F. hepatica are RNAi competent. RNAi effector analyses supported growing evidence that parasitic flatworms have evolved a separate clade of RNAi effectors with unknown function. Secondly, we assessed the impact of growth / development during in vitro culture on RNAi in F. hepatica juveniles and found that during the first week post-excystment liver fluke juveniles exhibit quantitatively lower RNAi mediated transcript knockdown when maintained in growth inducing media. This did not appear to occur in older in vitro juveniles, suggesting that rapidly shifting transcript dynamics over the first week following excystment alters RNAi efficacy after a single 24 hour exposure to double stranded (ds)RNA. Finally, RNAi efficiency was found to be improved through use of a repeated dsRNA exposure methodology that has facilitated silencing of genes in a range of tissues, thereby increasing the utility of RNAi as a functional genomics tool in F. hepatica.

scholarly journals Acquired immune heterogeneity and its sources in human helminth infection

Parasitology ◽  
2010 ◽  
Vol 138 (2) ◽  
pp. 139-159 ◽  
Author(s):  
C. D. BOURKE ◽  
R. M. MAIZELS ◽  
F. MUTAPI
Keyword(s):  
Immune Responses ◽  
Large Scale ◽  
Antigen Expression ◽  
Epidemiological Studies ◽  
Public Health Importance ◽  
Host Immune Responses ◽  
Parasitic Worm ◽  
Acquired Immune Responses ◽  
The Impact

SUMMARYSimilarities in the immunobiology of different parasitic worm infections indicate that co-evolution of humans and helminths has shaped a common anti-helminth immune response. However, recentin vitroand immuno-epidemiological studies highlight fundamental differences and plasticity within host-helminth interactions. The ‘trade-off’ between immunity and immunopathology inherent in host immune responses occurs on a background of genetic polymorphism, variable exposure patterns and infection history. For the parasite, variation in life-cycle and antigen expression can influence the effector responses directed against them. This is particularly apparent when comparing gastrointestinal and tissue-dwelling helminths. Furthermore, insights into the impact of anti-helminthic treatment and co-infection on acquired immunity suggest that immune heterogeneity arises not from hosts and parasites in isolation, but also from the environment in which immune responses develop. Large-scale differences observed in the epidemiology of human helminthiases are a product of complex host-parasite-environment interactions which, given potential for exposure to parasite antigensin utero, can arise even before a parasite interacts with its human host. This review summarizes key differences identified in human acquired immune responses to nematode and trematode infections of public health importance and explores the factors contributing to these variations.

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