scholarly journals Comparison of Protective Immune Responses to Apicomplexan Parasites

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Sonja Frölich ◽  
Rolf Entzeroth ◽  
Michael Wallach

Members of the phylum Apicomplexa, which includes the speciesPlasmodium, Eimeria,Toxoplasma,andBabesiaamongst others, are the most successful intracellular pathogens known to humankind. The widespread acquisition of antimicrobial resistance to most drugs used to date has sparked a great deal of research and commercial interest in the development of vaccines as alternative control strategies. A few antigens from the asexual and sexual stages of apicomplexan development have been identified and their genes characterised; however, the fine cellular and molecular details of the effector mechanisms crucial for parasite inhibition and stimulation of protective immunity are still not entirely understood. This paper provides an overview of what is currently known about the protective immune response against the various types of apicomplexan parasites and focuses mainly on the similarities of these pathogens and their host interaction. Finally, the evolutionary relationships of these parasites and their hosts, as well as the modulation of immune functions that are critical in determining the outcome of the infection by these pathogenic organisms, are discussed.

2012 ◽  
Vol 209 (8) ◽  
pp. 1437-1444 ◽  
Author(s):  
R. William DePaolo ◽  
Karishma Kamdar ◽  
Samira Khakpour ◽  
Yui Sugiura ◽  
Wenxia Wang ◽  
...  

The balance between regulatory and inflammatory immune responses is critical to maintain intestinal homeostasis. Furthermore, the nature of the inflammatory response needs to be tailored to the tissue to provide proper protective immunity while preserving host integrity. TLR2 (Toll-like receptor 2) is a unique TLR in that it has been shown to promote regulatory and inflammatory T cell responses. Using Yersinia enterocolitica, we show that oral infection promotes TH17 immunity, whereas systemic infection promotes TH1 immunity. Furthermore, induction of TH17 immunity during oral infection is dependent on TLR1 and results from the combinatorial effect of TLR2/TLR1-induced IL-6 and IL-23 and the presence of TGF-β in the intestinal environment. Interestingly, TLR2/TLR1 was not involved in TH1 immune responses during systemic infection, whereas the TLR2/TLR6 receptor complex induced IL-10+ regulatory T cell responses during both systemic and oral infections. Our results reveal that the route of infection is central in determining which pathways provide protective immunity. Furthermore, they also demonstrate that TLR2 has dual immune functions in the gut and identify TLR1 as a critical innate receptor for protective intestinal TH17 immunity.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Meng Wang ◽  
Xiao-Yu Yang ◽  
Nian-Zhang Zhang ◽  
De-Lin Zhang ◽  
Xing-Quan Zhu

Toxoplasma gondiiis an obligate intracellular parasitic protozoan that can infect almost all species of warm-blooded animals. As any chemical-based drugs could not act against the tissue cyst stage ofT. gondii, vaccination may be one of the ideal control strategies. In the present study, two new vaccine candidates, named TgENO2 and TgTrxLp, were purified fromEscherichia coliwith pET-30a(+) expression system and then were injected into BALB/c mice to evaluate the protective efficacy against acute and chronic toxoplasmosis. The results showed that both the recombinant proteins, either alone or in combination, could elicit strong humoral and cellular immune responses with a higher level of IgG antibodies, IFN-γ, IL-2, CD4+, and CD8+T cells as compared to those in mice from control groups. After acute challenge with tachyzoites of the GJS strain, mice immunized with rTgTrxLp (8±2.77 d), rTgENO2 (7.4±1.81 d), and rTgTrxLp + rTgENO2 (8.38±4.57 d) proteins showed significantly longer survival time than those that received Freund’s adjuvant (6.78±2.08 d) and PBS (6.38±4.65 d) (χ2= 9.687, df = 4,P=0.046). The protective immunity of rTgTrxLp, rTgENO2, and rTgTrxLp + rTgENO2 proteins against chronicT. gondiiinfection showed 69.77%, 58.14%, and 20.93% brain cyst reduction as compared to mice that received PBS. The present study suggested that both TgENO2 and TgTrxLp were potential candidates for the development of multicomponent vaccines against toxoplasmosis.


1987 ◽  
Vol 165 (3) ◽  
pp. 799-811 ◽  
Author(s):  
R F Breiman ◽  
M A Horwitz

We have employed the guinea pig model of L. pneumophila infection, which mimics Legionnaires' disease in humans both clinically and pathologically, to study humoral and cell-mediated immune responses to L. pneumophila and to examine protective immunity after aerosol exposure, the natural route of infection. Guinea pigs exposed to sublethal concentrations of L. pneumophila by aerosol developed strong humoral immune responses. By the indirect fluorescent antibody assay, exposed guinea pigs had a median serum antibody titer (expressed as the reciprocal of the highest positive dilution) of 32, whereas control guinea pigs had a median titer of less than 1. Sublethally infected (immunized) guinea pigs also developed strong cell-mediated immune responses. In response to L. pneumophila antigens, splenic lymphocytes from immunized but not control animals proliferated strongly in vitro, as measured by their capacity to incorporate [3H]thymidine. Moreover, immunized but not control guinea pigs developed strong cutaneous delayed-type hypersensitivity to intradermally injected L. pneumophila antigens. Sublethally infected (immunized) guinea pigs exhibited strong protective immunity to L. pneumophila. In two independent experiments, all 22 immunized guinea pigs survived aerosol challenge with one or three times the lethal dose of L. pneumophila whereas none of 16 sham-immunized control guinea pigs survived (p less than 0.0001 in each experiment). Immunized guinea pigs were not protected significantly from challenge with 10 times the lethal dose. Immunized but not control animals cleared the bacteria from their lungs. This study demonstrates that guinea pigs sublethally infected with L. pneumophila by the aerosol route develop strong humoral immune responses to this pathogen, develop strong cell-mediated immune responses and cutaneous delayed-type hypersensitivity to L. pneumophila antigens, are protected against subsequent lethal aerosol challenge, and are able to clear the bacteria from their lungs. The guinea pig model of L. pneumophila pulmonary infection is as an excellent one for studying general principles of host defense against pulmonary infections caused by intracellular pathogens.


2020 ◽  
Vol 22 (1) ◽  
pp. 44
Author(s):  
Marc Micó-Carnero ◽  
Carlos Rojano-Alfonso ◽  
Ana Isabel Álvarez-Mercado ◽  
Jordi Gracia-Sancho ◽  
Araní Casillas-Ramírez ◽  
...  

Microbiota is defined as the collection of microorganisms within the gastrointestinal ecosystem. These microbes are strongly implicated in the stimulation of immune responses. An unbalanced microbiota, termed dysbiosis, is related to the development of several liver diseases. The bidirectional relationship between the gut, its microbiota and the liver is referred to as the gut–liver axis. The translocation of bacterial products from the intestine to the liver induces inflammation in different cell types such as Kupffer cells, and a fibrotic response in hepatic stellate cells, resulting in deleterious effects on hepatocytes. Moreover, ischemia-reperfusion injury, a consequence of liver surgery, alters the microbiota profile, affecting inflammation, the immune response and even liver regeneration. Microbiota also seems to play an important role in post-operative outcomes (i.e., liver transplantation or liver resection). Nonetheless, studies to determine changes in the gut microbial populations produced during and after surgery, and affecting liver function and regeneration are scarce. In the present review we analyze and discuss the preclinical and clinical studies reported in the literature focused on the evaluation of alterations in microbiota and its products as well as their effects on post-operative outcomes in hepatic surgery.


2010 ◽  
Vol 38 (01) ◽  
pp. 173-190 ◽  
Author(s):  
Hui-Fen Liao ◽  
Min-Chi Lu ◽  
Hon-Chou Chang ◽  
Cheng-Chung Wei ◽  
Chih-Hsiung Kao ◽  
...  

The Chinese medicinal herbs Radix Isatidis and Viola yedoensis Makino have been suggested to possess antiviral activity. This study tests whether these and other Chinese and Western herbal medicinal formulas can modulate the immune functions involving virus-suppression in BALB/c mouse. We first confirmed the extract from Viola yedoensis Makino, but not from Radix Isatidis, the traditional Chinese medicine (TCM) formula Chui-Uren-Chien (CUC), or a Western homeopathic medicinal drink Método Canova, could inhibit the replications of herpes simplex virus-1 and enterovirus 71 in the human neuroblastoma SK-N-SH cell line. Subsequently, the same herbal extracts and drink underwent toxicity and immunomodulatory tests on mice of 5–7 weeks old. After 8 weeks of feeding different herbal medicinal formulas, no hepatic or renal toxicity was noted in any tested animal; whereas among the immune function evaluations, only the mice treated with CUC extract were found to be associated with significant increases (p < 0.05) in both the level of plasma IgG and the percentage of monocyte in blood mononuclear cells as well as the activation of macrophage Raw264.7 cells for nitric oxide production, suggesting its role in modulating the non-specific immune response. Analyses using protein arrays showed CUC was the most potent herbal medicinal formula eliciting fluctuations in plasma cytokine and chemokine concentrations. Taking all experimental data together, we conclude Chui-Uren-Chien possesses immunomodulatory capability in mouse, but none of the herbal medicinal formulas tested here are involved in strengthening antiviral immunity.


2015 ◽  
Vol 89 (23) ◽  
pp. 12118-12130 ◽  
Author(s):  
Ferdinand Roesch ◽  
Léa Richard ◽  
Réjane Rua ◽  
Françoise Porrot ◽  
Nicoletta Casartelli ◽  
...  

ABSTRACTThe HIV-1 accessory protein Vpr displays different activities potentially impacting viral replication, including the arrest of the cell cycle in the G2phase and the stimulation of apoptosis and DNA damage response pathways. Vpr also modulates cytokine production by infected cells, but this property remains partly characterized. Here, we investigated the effect of Vpr on the production of the proinflammatory cytokine tumor necrosis factor (TNF). We report that Vpr significantly increases TNF secretion by infected lymphocytes.De novoproduction of Vpr is required for this effect. Vpr mutants known to be defective for G2cell cycle arrest induce lower levels of TNF secretion, suggesting a link between these two functions. Silencing experiments and the use of chemical inhibitors further implicated the cellular proteins DDB1 and TAK1 in this activity of Vpr. TNF secreted by HIV-1-infected cells triggers NF-κB activity in bystander cells and allows viral reactivation in a model of latently infected cells. Thus, the stimulation of the proinflammatory pathway by Vpr may impact HIV-1 replicationin vivo.IMPORTANCEThe role of the HIV-1 accessory protein Vpr remains only partially characterized. This protein is important for viral pathogenesis in infected individuals but is dispensable for viral replication in most cell culture systems. Some of the functions described for Vpr remain controversial. In particular, it remains unclear whether Vpr promotes or instead prevents proinflammatory and antiviral immune responses. In this report, we show that Vpr promotes the release of TNF, a proinflammatory cytokine associated with rapid disease progression. Using Vpr mutants or inhibiting selected cellular genes, we show that the cellular proteins DDB1 and TAK1 are involved in the release of TNF by HIV-infected cells. This report provides novel insights into how Vpr manipulates TNF production and helps clarify the role of Vpr in innate immune responses and inflammation.


2013 ◽  
Vol 81 (12) ◽  
pp. 4626-4634 ◽  
Author(s):  
Ediane B. Silva ◽  
Andrew Goodyear ◽  
Marjorie D. Sutherland ◽  
Nicole L. Podnecky ◽  
Mercedes Gonzalez-Juarrero ◽  
...  

ABSTRACTInfections with the Gram-negative bacteriumBurkholderia pseudomallei(melioidosis) are associated with high mortality, and there is currently no approved vaccine to prevent the development of melioidosis in humans. Infected patients also do not develop protective immunity to reinfection, and some individuals will develop chronic, subclinical infections withB. pseudomallei. At present, our understanding of what constitutes effective protective immunity againstB. pseudomalleiinfection remains incomplete. Therefore, we conducted a study to elucidate immune correlates of vaccine-induced protective immunity against acuteB. pseudomalleiinfection. BALB/c and C57BL/6 mice were immunized subcutaneously with a highly attenuated, Select Agent-excludedpurMdeletion mutant ofB. pseudomallei(strain Bp82) and then subjected to intranasal challenge with virulentB. pseudomalleistrain 1026b. Immunization with Bp82 generated significant protection from challenge withB. pseudomallei, and protection was associated with a significant reduction in bacterial burden in lungs, liver, and spleen of immunized mice. Humoral immunity was critically important for vaccine-induced protection, as mice lacking B cells were not protected by immunization and serum from Bp82-vaccinated mice could transfer partial protection to nonvaccinated animals. In contrast, vaccine-induced protective immunity was found to be independent of both CD4 and CD8 T cells. Tracking studies demonstrated uptake of the Bp82 vaccine strain predominately by neutrophils in vaccine-draining lymph nodes and by smaller numbers of dendritic cells (DC) and monocytes. We concluded that protection following cutaneous immunization with a live attenuatedBurkholderiavaccine strain was dependent primarily on generation of effective humoral immune responses.


2013 ◽  
Vol 1538 ◽  
pp. 116-125 ◽  
Author(s):  
Goutam Dutta ◽  
Ananda Raj Goswami ◽  
Tusharkanti Ghosh

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