scholarly journals Dairy Heifers Naturally Exposed toFasciola hepaticaDevelop a Type 2 Immune Response and Concomitant Suppression of Leukocyte Proliferation

2017 ◽  
Vol 86 (1) ◽  
Author(s):  
John Graham-Brown ◽  
Catherine Hartley ◽  
Helen Clough ◽  
Aras Kadioglu ◽  
Matthew Baylis ◽  
...  

ABSTRACTFasciola hepaticais a parasitic trematode of global importance in livestock. Control strategies reliant on anthelmintics are unsustainable due to the emergence of drug resistance. Vaccines are under development, but efficacies are variable. Evidence from experimental infection suggests that vaccine efficacy may be affected by parasite-induced immunomodulation. Little is known about the immune response toF. hepaticafollowing natural exposure. Hence, we analyzed the immune responses over time in calves naturally exposed toF. hepaticainfection. Cohorts of replacement dairy heifer calves (n= 42) with no prior exposure toF. hepatica, on three commercial dairy farms, were sampled over the course of a grazing season. Exposure was determined through anF. hepatica-specific serum antibody enzyme-linked immunosorbent assay (ELISA) and fluke egg counts. Concurrent changes in peripheral blood leukocyte subpopulations, lymphocyte proliferation, and cytokine responses were measured. Relationships between fluke infection and immune responses were analyzed by using multivariable linear mixed-effect models. All calves from one farm showed evidence of exposure, while cohorts from the remaining two farms remained negative over the grazing season. A type 2 immune response was associated with exposure, with increased interleukin-4 (IL-4) production, IL-5 transcription, and eosinophilia. Suppression of parasite-specific peripheral blood mononuclear cell (PBMC) proliferation was evident, while decreased mitogen-stimulated gamma interferon (IFN-γ) production suggested immunomodulation, which was not restricted to parasite-specific responses. Our findings show that the global immune response is modulated toward a nonproliferative type 2 state following natural challenge withF. hepatica. This has implications in terms of the timing of the administration of vaccination programs and for host susceptibility to coinfecting pathogens.

2014 ◽  
Vol 134 (3) ◽  
pp. 671-678.e4 ◽  
Author(s):  
Kathleen R. Bartemes ◽  
Gail M. Kephart ◽  
Stephanie J. Fox ◽  
Hirohito Kita

2000 ◽  
Vol 68 (4) ◽  
pp. 1815-1819 ◽  
Author(s):  
Matthew D. Taylor ◽  
Catherine J. Betts ◽  
Kathryn J. Else

ABSTRACT The study of human cellular immune responses to parasite infection under field conditions is very complex. Often, the only practical site from which to sample the cellular responses is the peripheral blood. Sampling peripheral blood lymphocytes (PBL) relies on the assumption that these peripheral responses accurately reflect the immune responses acting locally at the site of infection. This is a particularly important point for the human intestinal helminth Trichuris trichiura, which solely inhabits the cecum and large intestine and so will stimulate a localized immune response. Using the well-defined model of T. trichiura, T. muris in the mouse, we have demonstrated that the dominant cytokine responses of the mesenteric lymph nodes (MLN) can be detected by sampling PBL. Resistant mice which mount a type 2 cytokine response in their MLN had PBL producing interleukin-4 (IL-4), IL-5, and IL-9, with negligible levels of gamma interferon (IFN-γ). Conversely, susceptible mice which mount a type 1 cytokine response in their MLN had PBL producing IFN-γ and negligible levels of type 2 cytokines. We have also shown that the PBL are capable of mounting a functional immune response against T. muris. PBL from immune mice were capable of transferring immunity to T. muris-infected severe combined immunodeficient (C.B-17 scid/scid) mice. Sampling PBL responses is therefore a viable option for monitoring human intestinal immune responses during T. trichiura infection in the field.


2019 ◽  
Author(s):  
Jesuthas Ajendra ◽  
Alistair L. Chenery ◽  
James E. Parkinson ◽  
Brian H. K. Chan ◽  
Stella Pearson ◽  
...  

ABSTRACTNippostrongylus brasiliensis is a well-defined model of type-2 immunity but the early lung-migrating phase is dominated by innate IL-17A production and neutrophilia. Using N. brasiliensis infection we confirm previous observations that Il17a-KO mice exhibit an impaired type-2 immune response. Neutrophil depletion and reconstitution studies demonstrated that neutrophils contribute to the subsequent eosinophilia but are not responsible for the ability of IL-17A to promote type-2 cytokine responses. Transcriptional profiling of the lung on day 2 of N. brasiliensis infection revealed an increased Ifnγ signature in the Il17a-KO mice confirmed by enhanced IFNγ protein production. Depletion of early IFNγ rescued type-2 immune responses in the Il17a-KO mice demonstrating that IL-17A-mediated suppression of IFNγ promotes type-2 immunity. Notably, when IL-17A was blocked later in infection, the type-2 response increased. IL-17A regulation of type-2 immunity was lung-specific and infection with Trichuris muris, revealed that IL-17A promotes a type-2 immune response in the lung even when a parasite lifecycle is restricted to the intestine. Together our data reveal IL-17A as a major regulator of pulmonary type-2 immunity which supports the development of a protective type-2 immune response but subsequently limits the magnitude of that response.


2011 ◽  
Vol 18 (9) ◽  
pp. 1447-1455 ◽  
Author(s):  
Jennifer T. Brisbin ◽  
Joshua Gong ◽  
Shahriar Orouji ◽  
Jessica Esufali ◽  
Amirul I. Mallick ◽  
...  

ABSTRACTCommensal microbes in the intestine are in constant interaction with host cells and play a role in shaping the immune system.Lactobacillus acidophilus,Lactobacillus reuteri, andLactobacillus salivariusare members of the chicken intestinal microbiota and have been shown to induce different cytokine profiles in mononuclear cellsin vitro. The objective of the present study was to examine the effects of these bacteria individually or in combination on the induction of antibody- and cell-mediated immune responsesin vivo. The birds received lactobacilli weekly via oral gavage starting on day of hatch and subsequently, at 14 and 21 days, were immunized with sheep red blood cells (SRBC), keyhole limpet hemocyanin (KLH), Newcastle disease virus vaccine, and infectious bursal disease virus vaccine. Antibody responses in serum were measured weekly for 4 weeks beginning on the day of primary immunization. The cell-mediated immune response was evaluated at 21 days postimmunization by measurement of gamma interferon (IFN-γ) production in splenocytes stimulated with inactivated vaccine antigens.L. salivarius-treated birds had significantly more serum antibody to SRBC and KLH than birds that were not treated with probiotics.L. salivarius-treated birds also had decreased cell-mediated immune responses to recall antigen stimulation.L. reuteritreatment did not significantly affect the systemic immune response, whileL. acidophilustreatment increased the antibody response to KLH. These results indicate that systemic antibody- and cell-mediated immune responses can be modulated by oral treatment with lactobacilli but that these bacteria may vary in their ability to modulate the immune response.


2019 ◽  
Vol 20 (21) ◽  
pp. 5493 ◽  
Author(s):  
Meunier ◽  
Chea ◽  
Garrido ◽  
Perchet ◽  
Petit ◽  
...  

Innate lymphoid cells (ILC) are important players of early immune defenses in situations like lymphoid organogenesis or in case of immune response to inflammation, infection and cancer. Th1 and Th2 antagonism is crucial for the regulation of immune responses, however mechanisms are still unclear for ILC functions. ILC2 and NK cells were reported to be both involved in allergic airway diseases and were shown to be able to interplay in the regulation of the immune response. CXCR6 is a common chemokine receptor expressed by all ILC, and its deficiency affects ILC2 and ILC1/NK cell numbers and functions in lungs in both steady-state and inflammatory conditions. We determined that the absence of a specific ILC2 KLRG1+ST2– subset in CXCR6-deficient mice is probably dependent on CXCR6 for its recruitment to the lung under inflammation. We show that despite their decreased numbers, lung CXCR6-deficient ILC2 are even more activated cells producing large amount of type 2 cytokines that could drive eosinophilia. This is strongly associated to the decrease of the lung Th1 response in CXCR6-deficient mice.


Cell ◽  
2021 ◽  
Author(s):  
Mark R. Cronan ◽  
Erika J. Hughes ◽  
W. Jared Brewer ◽  
Gopinath Viswanathan ◽  
Emily G. Hunt ◽  
...  

2013 ◽  
Vol 20 (11) ◽  
pp. 1703-1710 ◽  
Author(s):  
Luca Formichella ◽  
Laura Romberg ◽  
Christian Bolz ◽  
Michael Vieth ◽  
Michael Geppert ◽  
...  

ABSTRACTHelicobacter pyloricolonizes half of the world's population, and infection can lead to ulcers, gastric cancer, and mucosa-associated lymphoid tissue (MALT) lymphoma. Serology is the only test applicable for large-scale, population-based screening, but current tests are hampered by a lack of sensitivity and/or specificity. Also, no serologic test allows the differentiation of type I and type II strains, which is important for predicting the clinical outcome.H. pylorivirulence factors have been associated with disease, but direct assessment of virulence factors requires invasive methods to obtain gastric biopsy specimens. Our work aimed at the development of a highly sensitive and specific, noninvasive serologic test to detect immune responses to importantH. pylorivirulence factors. This line immunoassay system (recomLine) is based on recombinant proteins. For this assay, six highly immunogenic virulence factors (CagA, VacA, GroEL, gGT, HcpC, and UreA) were expressed inEscherichia coli, purified, and immobilized to nitrocellulose membranes to detect serological immune responses in patient's sera. For the validation of the line assay, a cohort of 500 patients was screened, of which 290 (58.0%) wereH. pylorinegative and 210 (42.0%) were positive by histology. The assay showed sensitivity and specificity of 97.6% and 96.2%, respectively, compared to histology. In direct comparison to lysate blotting and enzyme-linked immunosorbent assay (ELISA), therecomLine assay had increased discriminatory power. For the assessment of individual risk for gastrointestinal disease, the test must be validated in a larger and defined patient cohort. Taking the data together, therecomLine assay provides a valuable tool for the diagnosis ofH. pyloriinfection.


Author(s):  
Mounir M El-safty ◽  
Hala Mahmoud ◽  
Eman Sa Zaki ◽  
Howaida I Abd-alla

  Objective: Salmonella enteritidis ghosts (SEGs) is a non-living empty bacterial cell envelopes which were generated using a different concentration of sodium hydroxide (NaOH) 6.4 mg/mL and evaluated as a vaccine candidate in specific pathogen-free (SPF) chicken. SEGs have been produced by chemical-mediated lysis and evaluated the potential efficacy of chemically induced SEG vaccine and its ability to induce protective immune responses against virulent S. enteritidis challenge in SPF chickens.Methods: SPF chickens were divided into three groups: Group A (non-vaccinated control), Group B (vaccinated with prepared vaccine), and Group C (vaccinated with commercial vaccine).Results: Vaccination of SPF chicken with SEGs induced higher immune responses before and after virulent challenge. SPF chicken vaccinated with SEGs showed increasing in serum enzyme-linked immunosorbent assay (ELISA) antibodies. During the vaccination period, Groups B and C showed higher serum antibody titer compared to Group A. The minimal inhibitory concentration (MIC) of NaOH was capable of inducing non-living SEGs, and it has successfully generated non-living SEGs by MIC of NaOH.Conclusion: It is a one-step process which means easy manufacturing and low production cost compared to protein E-mediated lysis method. Chemically induced SEG vaccine is a highly effective method for inducing protective immunity. This study strongly suggests that SEGs will be a permissive vaccine, as the method of inhibition of S. enteritidis was safe and cheaper than other methods, and it gave a good protection.


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