Modulation of a Heterologous Immune Response by the Products of Ascaris suum

ABSTRACT Helminth infections are among the most potent stimulators of Th2-type immune responses and have been widely demonstrated to modify responsiveness to both nonparasite antigens and other infectious agents in a nonspecific manner in infected animals. We investigated the immunomodulatory properties of pseudocoelomic body fluid from adult Ascaris suum gastrointestinal helminths (ABF) and its defined allergen (ABA-1) by examining their effects on the immune response to a heterologous antigen, ovalbumin. Our results indicate that ABF has potent immunomodulatory activity and that the effects observed are consistent with skewing towards a Th2-type response rather than induction of anergy. Our findings show that the immunomodulatory activities of ABF are associated with components other than the major constituent and putative allergen, ABA-1. Furthermore, the allergic responses to ABA-1 are not a result of an intrinsic allergenicity of the protein but are more a reflection of the wider induction of a Th2 response by the infection. Importantly, the induction of interleukin-10 by ABF also suggests that T regulatory cells may play a role in immunomodulation of immune responses by parasitic helminths.

Download Full-text

The Mycobacterium tuberculosis Recombinant 27-Kilodalton Lipoprotein Induces a Strong Th1-Type Immune Response Deleterious to Protection

Infection and Immunity ◽

10.1128/iai.71.6.3146-3154.2003 ◽

2003 ◽

Vol 71 (6) ◽

pp. 3146-3154 ◽

Cited By ~ 55

Author(s):

Avi-Hai Hovav ◽

Jacob Mullerad ◽

Liuba Davidovitch ◽

Yolanta Fishman ◽

Fabiana Bigi ◽

...

Keyword(s):

Immune Response ◽

Mycobacterium Tuberculosis ◽

Immune Responses ◽

Interleukin 10 ◽

Control Groups ◽

Cellular Immune Responses ◽

Protective Antigens ◽

Proliferation Response ◽

Cellular Immune ◽

Mycobacterial Antigens

ABSTRACT Th1 immune response is essential in the protection against mycobacterial intracellular pathogens. Lipoproteins trigger both humoral and cellular immune responses and may be candidate protective antigens. We studied in BALB/c mice the immunogenicity and the protection offered by the recombinant 27-kDa Mycobacterium tuberculosis lipoprotein and the corresponding DNA vaccine. Immunization with the 27-kDa antigen resulted in high titers of immunoglobulin G1 (IgG1) and IgG2a with a typical Th1 profile and a strong delayed hypersensitivity response. A strong proliferation response was observed in splenocytes, and significant nitric oxide production and gamma interferon secretion but not interleukin 10 secretion were measured. Based on these criteria, the 27-kDa antigen induced a typical Th1-type immune response thought to be necessary for protection. Surprisingly, in 27-kDa-vaccinated mice (protein or DNA vaccines) challenged by M. tuberculosis H37Rv or BCG strains, there was a significant increase in the numbers of CFU in the spleen compared to that for control groups. Furthermore, the protection provided by BCG or other mycobacterial antigens was completely abolished once the 27-kDa antigen was added to the vaccine preparations. This study indicates that the 27-kDa antigen has an adverse effect on the protection afforded by recognized vaccines. We are currently studying how the 27-kDa antigen modulates the mouse immune response.

Download Full-text

JP-8 jet fuel exposure suppresses the immune response to viral infections

Toxicology and Industrial Health ◽

10.1177/0748233708093781 ◽

2008 ◽

Vol 24 (4) ◽

pp. 209-216 ◽

Cited By ~ 5

Author(s):

DT Harris ◽

D Sakiestewa ◽

D Titone ◽

X He ◽

J Hyde ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Viral Infection ◽

Viral Infections ◽

Immune Cell ◽

Immunosuppressive Agents ◽

Interleukin 10 ◽

Jet Fuel ◽

Us Air Force ◽

Influenza Viral Infection

The US Air Force has implemented the widespread use of JP-8 jet fuel in its operations, although a thorough understanding of its potential effects upon exposed personnel is unclear. Previous work has reported that JP-8 exposure is immunosuppressive. Exposure of mice to JP-8 for 1 h/day resulted in immediate secretion of two immunosuppressive agents, namely, interleukin-10 and prostaglandin E2. Thus, it was of interest to determine if jet fuel exposure might alter the immune response to infectious agents. The Hong Kong influenza model was used for these studies. Mice were exposed to 1000 mg/m3 JP-8 (1 h/day) for 7 days before influenza viral infection. Animals were infected intra-nasally with virus and followed in terms of overall survival as well as immune responses. All surviving animals were killed 14 days after viral infection. In the present study, JP-8 exposure increased the severity of the viral infection by suppressing the anti-viral immune responses. That is, exposure of mice to JP-8 for 1 h/day for 7 days before infection resulted in decreased immune cell viability after exposure and infection, a greater than fourfold decrease in immune proliferative responses to mitogens, as well as an overall loss of CD3+, CD4+, and CD8+ T cells from the lymph nodes, but not the spleens, of infected animals. These changes resulted in decreased survival of the exposed and infected mice, with only 33% of animals surviving as compared with 50% of mice infected but not jet fuel–exposed (and 100% of mice exposed only to JP-8). Thus, short-term, low-concentration JP-8 jet fuel exposures have significant suppressive effects on the immune system which can result in increased severity of viral infections.

Download Full-text

Cysticercus cellulosae Regulates T-Cell Responses and Interacts With the Host Immune System by Excreting and Secreting Antigens

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.728222 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xianmin Fan ◽

Yue Zhang ◽

Renhui Ouyang ◽

Bo Luo ◽

Lizhu Li ◽

...

Keyword(s):

Immune Response ◽

T Cell ◽

Immune Responses ◽

Cytokine Production ◽

Host Immune Response ◽

Interleukin 10 ◽

Host Immune System ◽

Cell Responses ◽

Cysticercus Cellulosae ◽

T Cell Immune Responses

Cysticercus cellulosae (C. cellulosae) excretes and secretes antigens during the parasitic process to regulate the host immune response; however, resulting immune response and cytokine production in the host during infection still remains unclear. We used C. cellulosae crude antigens (CAs) as controls to explore the effect of excretory secretory antigens (ESAs) on T-cell immune responses in piglets. C. cellulosae ESAs induced imbalanced CD4+/CD8+ T-cell proportions, increased the CD4+Foxp3+ and CD8+Foxp3+ T-cell frequencies, and induced lymphocytes to produce interleukin-10, which was mainly attributed to CD4+ and CD4−CD8− T cells. The ESAs also induced Th2-type immune responses. The results showed that the ability of C. cellulosae to escape the host immune attacks and establish a persistent infection may be related to host immune response regulation by the ESAs.

Download Full-text

Interleukin-10 and Immunity against Prokaryotic and Eukaryotic Intracellular Pathogens

Infection and Immunity ◽

10.1128/iai.00047-11 ◽

2011 ◽

Vol 79 (8) ◽

pp. 2964-2973 ◽

Cited By ~ 123

Author(s):

Joshua C. Cyktor ◽

Joanne Turner

Keyword(s):

Immune Response ◽

Immune Responses ◽

Inflammatory Responses ◽

Interleukin 10 ◽

Parasitic Infections ◽

Intracellular Pathogens ◽

Effective Immune Response ◽

Infection Models ◽

And Function

ABSTRACTThe generation of an effective immune response against an infection while also limiting tissue damage requires a delicate balance between pro- and anti-inflammatory responses. Interleukin-10 (IL-10) has potent immunosuppressive effects and is essential for regulation of immune responses. However, the immunosuppressive properties of IL-10 can also be exploited by pathogens to facilitate their own survival. In this minireview, we discuss the role of IL-10 in modulating intracellular bacterial, fungal, and parasitic infections. Using information from several different infection models, we bring together and highlight some common pathways for IL-10 regulation and function that cannot be fully appreciated by studies of a single pathogen.

Download Full-text

Immunization by Replication-Competent Controlled Herpesvirus Vectors

Journal of Virology ◽

10.1128/jvi.00616-18 ◽

2018 ◽

Vol 92 (16) ◽

Cited By ~ 1

Author(s):

David C. Bloom ◽

Robert K. Tran ◽

Joyce Feller ◽

Richard Voellmy

Keyword(s):

Immune Response ◽

Immune Responses ◽

Viral Vectors ◽

Wild Type Virus ◽

Wild Type ◽

Equine Influenza Virus ◽

Heterologous Antigen ◽

Equine Influenza ◽

Cellular Immune ◽

Gene Switch

ABSTRACT Replication-competent controlled virus vectors were derived from the virulent herpes simplex virus 1 (HSV-1) wild-type strain 17syn+ by placing one or two replication-essential genes under the stringent control of a gene switch that is coactivated by heat and an antiprogestin. Upon activation of the gene switch, the vectors replicate in infected cells with an efficacy that approaches that of the wild-type virus from which they were derived. Essentially no replication occurs in the absence of activation. When administered to mice, localized application of a transient heat treatment in the presence of systemic antiprogestin results in efficient but limited virus replication at the site of administration. The immunogenicity of these viral vectors was tested in a mouse footpad lethal challenge model. Unactivated viral vectors—which may be regarded as equivalents of inactivated vaccines—induced detectable protection against lethality caused by wild-type virus challenge. Single activation of the viral vectors at the site of administration (rear footpads) greatly enhanced protective immune responses, and a second immunization resulted in complete protection. Once activated, vectors also induced far better neutralizing antibody and HSV-1-specific cellular immune responses than unactivated vectors. To find out whether the immunogenicity of a heterologous antigen was also enhanced in the context of efficient transient vector replication, a virus vector constitutively expressing an equine influenza virus hemagglutinin was constructed. Immunization of mice with this recombinant induced detectable antibody-mediated neutralization of equine influenza virus, as well as a hemagglutinin-specific cellular immune response. Single activation of viral replication resulted in a severalfold enhancement of these immune responses. IMPORTANCE We hypothesized that vigorous replication of a pathogen may be critical for eliciting the most potent and balanced immune response against it. Hence, attenuation/inactivation (as in conventional vaccines) should be avoided. Instead, the necessary safety should be provided by placing replication of the pathogen under stringent control and by activating time-limited replication of the pathogen strictly in an administration region in which pathology cannot develop. Immunization will then occur in the context of highly efficient pathogen replication and uncompromised safety. We found that localized activation in mice of efficient but limited replication of a replication-competent controlled herpesvirus vector resulted in a greatly enhanced immune response to the virus or an expressed heterologous antigen. This finding supports the above-mentioned hypothesis and suggests that the vectors may be promising novel agents worth exploring for the prevention/mitigation of infectious diseases for which efficient vaccination is lacking, in particular in immunocompromised patients.

Download Full-text

Humoral immune responses induced by Gymnorhynchus gigas extracts in BALB/c mice

Journal of Helminthology ◽

10.1017/s0022149x99000372 ◽

1999 ◽

Vol 73 (3) ◽

pp. 239-243 ◽

Cited By ~ 10

Author(s):

M. Rodero ◽

C. Cuéllar

Keyword(s):

Immune Response ◽

Immune Responses ◽

Humoral Immune Response ◽

Type I ◽

Igg Antibody ◽

Th2 Response ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Antibody Class ◽

Allergic Disorders

The aim of this study was to determine if the plerocercoid larvae of Gymnorhynchus gigas, a common cestode of the ray’s bream (Brama raii), possess antigenic compounds potentially capable of provoking anaphylactic episodes. A murine experimental model, using BALB/c mice, was developed to study the humoral immune response induced by G. gigas extracts. A highly specific humoral immune response was detected and cross-reactions were not observed between parasite and host antigens. The presence of IgM and IgG3 levels suggest the presence of thymus-independent antigens in the parasitic extract. The IgG antibody class showed the highest levels, with the IgG1 the predominant subclass. These IgG1 levels are in accordance with the supposed presence of a type I allergic reaction after the ingestion of G. gigas plerocercoids parasitizing fish, as well as inducing anaphylaxia in fish. These results indicate that somatic products released from ingested larvae of G. gigas could induce the development of a Th2 response capable of causing allergic disorders.

Download Full-text

Immunosuppressory activity of the cyclodimeric peptide with RGD-sequences.

Acta Biochimica Polonica ◽

10.18388/abp.2001_5118 ◽

2001 ◽

Vol 48 (1) ◽

pp. 121-130 ◽

Cited By ~ 9

Author(s):

Z Szewczuk ◽

P Buczek ◽

P Stefanowicz ◽

K Krajewski ◽

Z Wieczorek ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Immunological Response ◽

Immunomodulatory Activity ◽

Design And Synthesis ◽

Cellular Immune Responses ◽

Rgd Sequence ◽

Hla Dq ◽

Cellular Immune ◽

Nonapeptide Fragment

Our previous studies showed that the nonapeptide fragment of HLA-DQ of the sequence H-Thr-Pro-Gln-Arg-Gly-Asp-Val-Tyr-Thr-OH, located in the beta164-172 loop, strongly suppresses the humoral and cellular immune responses, while its shorter analogs, H-Arg-Gly-Asp-Val-OH, H-Arg-Gly-Asp-Val-Tyr-OH and H-Gln-Arg-Gly-Asp-Val-Tyr-OH show only a weak stimulatory activity in respect to the humoral immunological response. These fragments contain the Arg-Gly-Asp (RGD) sequence, known for its importance for cellular association phenomena. Based on the crystal structure of HLA-DR1, we also designed and synthesized a cyclic analog H-Cys-Arg-Gly-Asp-Val-Tyr-Cys-OH with restricted conformation, which strongly suppresses the immune response and selectively inhibits the alphavbeta3 integrin, suggesting that the mechanism of the immunosuppressory action of the peptide is associated with inhibition of the integrin. In this paper we present the design and synthesis of the cyclodimeric peptide, Arg-Gly-Asp-Arg-Gly-Asp, which is also known as a selective alphavbeta3 inhibitor. The synthesized peptide strongly suppresses both the humoral and cellular immune response. The results support our hypothesis that the immunomodulatory activity of HLA-DQ fragments may be connected with their interactions with some particular integrins on the cell surface.

Download Full-text

Difluoromethylornithine (DFMO), an Inhibitor of Polyamine Biosynthesis, and Antioxidant N-Acetylcysteine Potentiate Immune Response in Mice to the Recombinant Hepatitis C Virus NS5B Protein

International Journal of Molecular Sciences ◽

10.3390/ijms22136892 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6892

Author(s):

Ekaterina I. Lesnova ◽

Olga V. Masalova ◽

Kristina Yu. Permyakova ◽

Vyacheslav V. Kozlov ◽

Tatyana N. Nikolaeva ◽

...

Keyword(s):

Immune Response ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Suppressor Cells ◽

Interleukin 10 ◽

Interferon Γ ◽

Immunomodulatory Activity ◽

Polyamine Biosynthesis ◽

Ifn Γ ◽

Ns5b Protein

Hepatitis C virus (HCV) is one of the main triggers of chronic liver disease. Despite tremendous progress in the HCV field, there is still no vaccine against this virus. Potential vaccines can be based on its recombinant proteins. To increase the humoral and, especially, cellular immune response to them, more effective adjuvants are needed. Here, we evaluated a panel of compounds as potential adjuvants using the HCV NS5B protein as an immunogen. These compounds included inhibitors of polyamine biosynthesis and urea cycle, the mTOR pathway, antioxidants, and cellular receptors. A pronounced stimulation of cell proliferation and interferon-γ (IFN-γ) secretion in response to concanavalin A was shown for antioxidant N-acetylcysteine (NAC), polyamine biosynthesis inhibitor 2-difluoromethylornithine (DFMO), and TLR9 agonist CpG ODN 1826 (CpG). Their usage during the immunization of mice with the recombinant NS5B protein significantly increased antibody titers, enhanced lymphocyte proliferation and IFN-γ production. NAC and CpG decreased relative Treg numbers; CpG increased the number of myeloid-derived suppressor cells (MDSCs), whereas neither NAC nor DFMO affected MDSC counts. NAC and DFMO suppressed NO and interleukin 10 (IL-10) production by splenocytes, while DFMO increased the levels of IL-12. This is the first evidence of immunomodulatory activity of NAC and DFMO during prophylactic immunization against infectious diseases.

Download Full-text

Inhibition of Autoimmune Type 1 Diabetes by Gastrointestinal Helminth Infection

Infection and Immunity ◽

10.1128/iai.00664-06 ◽

2006 ◽

Vol 75 (1) ◽

pp. 397-407 ◽

Cited By ~ 156

Author(s):

Karin A. Saunders ◽

Tim Raine ◽

Anne Cooke ◽

Catherine E. Lawrence

Keyword(s):

Immune Response ◽

Type 1 Diabetes ◽

Beta Cells ◽

Helminth Infection ◽

Trichinella Spiralis ◽

Autoimmune Diabetes ◽

Nod Mice ◽

Gastrointestinal Helminths ◽

Th2 Response

ABSTRACT Gastrointestinal nematode infections are prevalent worldwide and are potent inducers of T helper 2 responses with the capacity to modulate the immune response to heterologous antigens. Parasitic helminth infection has even been shown to modulate the immune response associated with autoimmune diseases. Nonobese diabetic (NOD) mice provide a model for studying human autoimmune diabetes; as in humans, the development of diabetes in NOD mice has been linked to the loss of self-tolerance to beta cell autoantigens. Previous studies with the NOD mouse have shown that helminth and bacterial infection appears to inhibit type 1 diabetes by disrupting the pathways leading to the Th1-mediated destruction of insulin-producing beta cells. The aim of our study was to examine whether infection with the gastrointestinal helminths Trichinella spiralis or Heligmosomoides polygyrus could inhibit the development of autoimmune diabetes in NOD mice and to analyze the mechanisms involved in protection and the role of Th2 responses. Protection from diabetes was afforded by helminth infection, appeared to inhibit autoimmune diabetes by disrupting pathways leading to the destruction of beta cells, and was mediated by seemingly independent mechanisms depending on the parasite but which may be to be related to the capacity of the host to mount a Th2 response.

Download Full-text

Infection with the Helminth Nippostrongylus brasiliensis Does Not Interfere with Efficient Elimination of Mycobacterium bovis BCG from the Lungs of Mice

Clinical and Vaccine Immunology ◽

10.1128/cdli.9.3.727-730.2002 ◽

2002 ◽

Vol 9 (3) ◽

pp. 727-730 ◽

Cited By ~ 11

Author(s):

Klaus J. Erb ◽

Claudia Trujillo ◽

Mike Fugate ◽

Heidrun Moll

Keyword(s):

Immune Response ◽

T Cells ◽

Immune Responses ◽

Mycobacterium Bovis ◽

Helminth Infection ◽

Nippostrongylus Brasiliensis ◽

Th2 Response ◽

Th2 Responses ◽

The Impact ◽

Th1 Immune Response

ABSTRACT Infection with Mycobacterium tuberculosis continues to be one of the major global health threats. Strong mycobacterium-specific Th1 immune responses correlate with protection, and decreased Th1 responses correlate with disease progression. In contrast, the impact of Th2 responses on the development of protective immune responses to mycobacteria remains unclear. To analyze whether ongoing Th2 responses present in the lung influence the development of a protective Th1 immune response to mycobacteria, we coinfected mice with the helminth Nippostrongylus brasiliensis and Mycobacterium bovis BCG. We found that the T cells from the lymph nodes of coinfected mice secreted significantly less gamma interferon than did the T cells from mice infected with M. bovis BCG after in vitro stimulation with purified protein from M. tuberculosis when 108 CFU of M. bovis BCG were used for the infection. This result indicates that the helminth infection reduced the Th1 immune response to the mycobacteria in the lung. However, mycobacterial clearance was not delayed in the coinfected animals. Importantly, the infection with BCG after the helminth infection did not reduce the helminth-induced Th2 response in the lung, ruling out the possibility that the lack of a reduction in bacterial clearance in the coinfected mice was due to a downmodulation of the helminth-induced Th2 response. Taken together, our results suggest that ongoing Th2 responses in the lung do not necessarily lead to increased susceptibility to mycobacterial infection.

Download Full-text