scholarly journals Infection with Syphacia obvelata (Pinworm) Induces Protective Th2 Immune Responses and Influences Ovalbumin-Induced Allergic Reactions

2006 ◽  
Vol 74 (10) ◽  
pp. 5926-5932 ◽  
Author(s):  
Chesney Michels ◽  
Prem Goyal ◽  
Natalie Nieuwenhuizen ◽  
Frank Brombacher
Keyword(s):  
Immune Responses ◽  
Cytokine Production ◽  
Dominant Role ◽  
Parasite Burden ◽  
Gastrointestinal Nematode ◽  
Experimental Models ◽  
Interleukin 4 ◽  
Th2 Response ◽  
Specific Immunoglobulin ◽  
Syphacia Obvelata

ABSTRACT Infections with pinworms are common in rodent animal facilities. In this study, we show the consequence of an outbreak in a transgenic barrier facility of infection by Syphacia obvelata, a murine pinworm gastrointestinal nematode. Immune responses were defined in experimental infection studies with BALB/c mice. Infection with S. obvelata induced a transient Th2-type immune response with elevated interleukin 4 (IL-4), IL-5, and IL-13 cytokine production and parasite-specific immunoglobulin G1 (IgG1). In contrast, BALB/c mice deficient in IL-13, IL-4/13, or the IL-4 receptor alpha chain showed chronic disease, with a >100-fold higher parasite burden, increased gamma interferon production, parasite-specific IgG2b, and a default Th2 response. Interestingly, infected IL-4−/− BALB/c mice showed only slightly elevated parasite burdens compared to the control mice, suggesting that IL-13 plays the dominant role in the control of S. obvelata. The influence that pinworm infection has on the allergic response to a dietary antigen was found to be important. Helminth-infected mice immunized against ovalbumin (Ova) elicited more severe anaphylactic shock with reduced Ova-specific IL-4 and IL-5 than did noninfected controls, demonstrating that S. obvelata infection is able to influence nonrelated laboratory experiments. The latter outcome highlights the importance of maintaining mice for use as experimental models under pinworm-free conditions.

scholarly journals Mucosal Adjuvant Properties of the Shigella Invasin Complex

2006 ◽  
Vol 74 (5) ◽  
pp. 2856-2866 ◽  
Author(s):  
Robert W. Kaminski ◽  
K. Ross Turbyfill ◽  
Edwin V. Oaks
Keyword(s):  
Immune Responses ◽  
Binding Capacity ◽  
Lymphoid Cells ◽  
Mucosal Vaccine ◽  
Vaccine Antigen ◽  
Interleukin 4 ◽  
Cell Binding ◽  
Th2 Response ◽  
Mucosal Adjuvant ◽  
Mucosal Antibody

ABSTRACT The Shigella invasin complex (Invaplex) is an effective mucosal vaccine capable of protecting against Shigella challenge in animal models. The major antigenic constituents of Invaplex are the Ipa proteins and lipopolysaccharide. The cell-binding capacity of the Ipa proteins prompted the investigation into the adjuvanticity of Invaplex. Using ovalbumin (OVA) as a model antigen, intranasal immunization with OVA combined with Invaplex was found to enhance anti-OVA serum immunoglobulin G (IgG) and IgA responses and induce OVA-specific mucosal antibody responses at sites located both proximal and distal to the immunization site. The immune responses induced with OVA and Invaplex were comparable in both magnitude and duration to the immune responses induced after immunization with OVA and cholera toxin. The OVA-specific immune response was characterized by high levels of serum IgG1 and increased production of interleukin-4 (IL-4), IL-5, or IL-10 from lymphoid cells of immunized animals, suggesting a Th2 response. In addition to enhancing the immunogenicity of OVA, Invaplex-specific immune responses were also induced, indicating the potential for the development of a combination vaccine consisting of Invaplex and other immunogens. Preexisting Invaplex-specific immunity did not interfere with the capacity to enhance the immunogenicity of a second, unrelated vaccine antigen, suggesting that Invaplex could be used as a mucosal adjuvant in multiple vaccine regimens.

scholarly journals TIM-1 and TIM-3 enhancement of Th2 cytokine production by mast cells

Blood ◽  
2007 ◽  
Vol 110 (7) ◽  
pp. 2565-2568 ◽  
Author(s):  
Susumu Nakae ◽  
Motoyasu Iikura ◽  
Hajime Suto ◽  
Hisaya Akiba ◽  
Dale T. Umetsu ◽  
...  
Keyword(s):  
T Cell ◽  
Mast Cells ◽  
Immune Responses ◽  
Cytokine Production ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
T Helper ◽  
Th2 Cytokine ◽  
Peritoneal Mast Cells

Members of the T-cell immunoglobulin– and mucin-domain–containing molecule (TIM) family have roles in T-cell–mediated immune responses. TIM-1 and TIM-2 are predominantly expressed on T helper type 2 (Th2) cells, whereas TIM-3 is preferentially expressed on Th1 and Th17 cells. We found that TIM-1 and TIM-3, but neither TIM-2 nor TIM-4, were constitutively expressed on mouse peritoneal mast cells and bone marrow–derived cultured mast cells (BMCMCs). After IgE + Ag stimulation, TIM-1 expression was down-regulated on BMCMCs, whereas TIM-3 expression was up-regulated. We also found that recombinant mouse TIM-4 (rmTIM-4), which is a ligand for TIM-1, as well as an anti–TIM-3 polyclonal Ab, can promote interleukin-4 (IL-4), IL-6, and IL-13 production without enhancing degranulation in BMCMCs stimulated with IgE + Ag. Moreover, the anti–TIM-3 Ab, but neither anti–TIM-1 Ab nor rmTIM-4, suppressed mast-cell apoptosis. These observations suggest that TIM-1 and TIM-3 may be able to influence T-cell–mediated immune responses in part through effects on mast cells.

scholarly journals Type 2 immunity induced by bladder extracellular matrix enhances corneal wound healing

2021 ◽  
Vol 7 (16) ◽  
pp. eabe2635
Author(s):  
Xiaokun Wang ◽  
Liam Chung ◽  
Joshua Hooks ◽  
David R. Maestas ◽  
Andriana Lebid ◽  
...  
Keyword(s):  
Wound Healing ◽  
Immune Responses ◽  
Smooth Muscle Actin ◽  
Treated Group ◽  
Interleukin 4 ◽  
Impaired Wound Healing ◽  
Urinary Bladder Matrix ◽  
Incomplete Healing ◽  
Haze Formation

The avascular nature of cornea tissue limits its regenerative potential, which may lead to incomplete healing and formation of scars when damaged. Here, we applied micro- and ultrafine porcine urinary bladder matrix (UBM) particulate to promote type 2 immune responses in cornea wounds. Results demonstrated that UBM particulate substantially reduced corneal haze formation as compared to the saline-treated group. Flow cytometry and gene expression analysis showed that UBM particulate suppressed the differentiation of corneal stromal cells into α-smooth muscle actin–positive (αSMA+) myofibroblasts. UBM treatments up-regulated interleukin-4 (IL-4) produced primarily by eosinophils in the wounded corneas and CD4+ T cells in draining lymph nodes, suggesting a cross-talk between local and peripheral immunity. Gata1−/− mice lacking eosinophils did not respond to UBM treatment and had impaired wound healing. In summary, stimulating type 2 immune responses in the wounded cornea can promote proregenerative environments that lead to improved wound healing for vision restoration.

scholarly journals Immunogenicity and protective efficacy of enterotoxigenic Escherichia coli (ETEC) total RNA against ETEC challenge in a mouse model

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mandi Liu ◽  
Yue Zhang ◽  
Di Zhang ◽  
Yun Bai ◽  
Guomei Liu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Mouse Model ◽  
Immune Responses ◽  
Protective Efficacy ◽  
Enterotoxigenic Escherichia Coli ◽  
Economic Losses ◽  
Th2 Response ◽  
Total Rna ◽  
Etec Infection

AbstractEnterotoxigenic Escherichia coli (ETEC), an essential cause of post-weaning diarrhea (PWD) in piglets, leads to significant economic losses to the pig industry. The present study aims to identify the role of ETEC total RNA in eliciting immune responses to protect animals against ETEC infection. The results showed that the total RNA isolated from pig-derived ETEC K88ac strain effectively stimulated the IL-1β secretion of porcine intestinal epithelial cells (IPEC-J2). The mouse model immunized with ETEC total RNA via intramuscular injection (IM) or oral route (OR) was used to evaluate the protective efficiency of the ETEC total RNA. The results suggested that 70 μg ETEC total RNA administered by either route significantly promoted the production of the serum IL-1β and K88ac specific immunoglobulins (IgG, IgM, and IgA). Besides, the ETEC RNA administration augmented strong mucosal immunity by elevating K88ac specific IgA level in the intestinal fluid. Intramuscularly administered RNA induced a Th1/Th2 shift toward a Th2 response, while the orally administered RNA did not. The ETEC total RNA efficiently protected the animals against the ETEC challenge either by itself or as an adjuvant. The histology characterization of the small intestines also suggested the ETEC RNA administration protected the small intestinal structure against the ETEC infection. Particularly of note was that the immunity level and protective efficacy caused by ETEC RNA were dose-dependent. These findings will help understand the role of bacterial RNA in eliciting immune responses, and benefit the development of RNA-based vaccines or adjuvants.

scholarly journals Ubiquitous Overexpression of Chromatin Remodeling Factor SRG3 Exacerbates Atopic Dermatitis in NC/Nga Mice by Enhancing Th2 Immune Responses

2021 ◽  
Vol 22 (4) ◽  
pp. 1553
Author(s):  
Sung Won Lee ◽  
Hyun Jung Park ◽  
Jungmin Jeon ◽  
Yun Hoo Park ◽  
Tae-Cheol Kim ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Mast Cells ◽  
Immune Responses ◽  
Chromatin Remodeling ◽  
Skin Diseases ◽  
Immunoglobulin E ◽  
Critical Role ◽  
Interleukin 4 ◽  
Inflammatory Skin Diseases ◽  
Immune Disorder

The SWItch (SWI)3-related gene (SRG3) product, a SWI/Sucrose Non-Fermenting (SNF) chromatin remodeling subunit, plays a critical role in regulating immune responses. We have previously shown that ubiquitous SRG3 overexpression attenuates the progression of Th1/Th17-mediated experimental autoimmune encephalomyelitis. However, it is unclear whether SRG3 overexpression can affect the pathogenesis of inflammatory skin diseases such as atopic dermatitis (AD), a Th2-type immune disorder. Thus, to elucidate the effects of SRG3 overexpression in AD development, we bred NC/Nga (NC) mice with transgenic mice where SRG3 expression is driven by the β-actin promoter (SRG3β-actin mice). We found that SRG3β-actin NC mice exhibit increased AD development (e.g., a higher clinical score, immunoglobulin E (IgE) hyperproduction, and an increased number of infiltrated mast cells and basophils in skin lesions) compared with wild-type NC mice. Moreover, the severity of AD pathogenesis in SRG3β-actin NC mice correlated with expansion of interleukin 4 (IL4)-producing basophils and mast cells, and M2 macrophages. Furthermore, this accelerated AD development is strongly associated with Treg cell suppression. Collectively, our results have identified that modulation of SRG3 function can be applied as one of the options to control AD pathogenesis.

scholarly journals Prediction of IL4 Inducing Peptides

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Sandeep Kumar Dhanda ◽  
Sudheer Gupta ◽  
Pooja Vir ◽  
G. P. S. Raghava
Keyword(s):  
Mhc Class Ii ◽  
Critical Role ◽  
Interleukin 4 ◽  
Th2 Response ◽  
Data Set ◽  
T Helper 2 ◽  
Cell Responses ◽  
Antibody Class ◽  
First Time ◽  
Motif Information

The secretion of Interleukin-4 (IL4) is the characteristic of T-helper 2 responses. IL4 is a cytokine produced by CD4+ T cells in response to helminthes and other extracellular parasites. It has a critical role in guiding antibody class switching, hematopoiesis and inflammation, and the development of appropriate effector T-cell responses. In this study, it is the first time an attempt has been made to understand whether it is possible to predict IL4 inducing peptides. The data set used in this study comprises 904 experimentally validated IL4 inducing and 742 noninducing MHC class II binders. Our analysis revealed that certain types of residues are preferred at certain positions in IL4 inducing peptides. It was also observed that IL4 inducing and noninducing epitopes differ in compositional and motif pattern. Based on our analysis we developed classification models where the hybrid method of amino acid pairs and motif information performed the best with maximum accuracy of 75.76% and MCC of 0.51. These results indicate that it is possible to predict IL4 inducing peptides with reasonable precession. These models would be useful in designing the peptides that may induce desired Th2 response.

scholarly journals Upregulated Expression of Cytotoxicity-Related Genes in IFN-γKnockout Mice withSchistosoma japonicumInfection

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Xiaotang Du ◽  
Jingjiao Wu ◽  
Meijuan Zhang ◽  
Yanan Gao ◽  
Donghui Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Schistosoma Japonicum ◽  
Fas Ligand ◽  
Acute Infection ◽  
Acquired Resistance ◽  
Parasite Burden ◽  
Cytotoxic T Cell ◽  
Igg Antibody

It is well accepted that IFN-γis important to the development of acquired resistance against murine schistosomiasis. However, thein vivorole of this immunoregulatory cytokine in helminth infection needs to be further investigated. In this study, parasite burden and host immune response were observed in IFN-γknockout mice (IFNg KO) infected withSchistosoma japonicumfor 6 weeks. The results suggested that deficiency in IFN-γled to decreased egg burden in mice, with low schistosome-specific IgG antibody response and enhanced activation of T cells during acute infection. Microarray and qRT-PCR data analyses showed significant upregulation of some cytotoxicity-related genes, including those from the granzyme family, tumor necrosis factor, Fas Ligand, and chemokines, in the spleen cells of IFNg KO mice. Furthermore, CD8+cells instead of NK cells of IFNg KO mice exhibited increased transcription of cytotoxic genes compared with WT mice. Additionally,Schistosoma japonicum-specific egg antigen immunization also could activate CD8+T cells to upregulate the expression of cytotoxic genes in IFNg KO mice. Our data suggest that IFN-γis not always a positive regulator of immune responses. In certain situations, the disruption of IFN-γsignaling may up-regulate the cytotoxic T-cell-mediated immune responses to the parasite.

scholarly journals Gender Is a Major Determinant of the Clinical Evolution and Immune Response in Hamsters Infected with Leishmania spp.

2002 ◽  
Vol 70 (5) ◽  
pp. 2288-2296 ◽  
Author(s):  
Bruno L. Travi ◽  
Yaneth Osorio ◽  
Peter C. Melby ◽  
Bysani Chandrasekar ◽  
Lourdes Arteaga ◽  
...  
Keyword(s):  
Immune Response ◽  
Transforming Growth Factor ◽  
Experimental Studies ◽  
Parasite Burden ◽  
Transforming Growth Factor Β ◽  
Lesion Size ◽  
Interleukin 4 ◽  
Cutaneous Lesions ◽  
Disease Evolution ◽  
Leishmania Spp

ABSTRACT In regions where leishmaniasis is endemic, clinical disease is usually reported more frequently among males than females. This difference could be due to disparate risks of exposure of males and females, but gender-related differences in the host response to infection may also play a role. Experimental studies of the influence of gender on Leishmania infection have not included parasites of the subgenus Viannia, which is the most common cause of cutaneous leishmaniasis in the Americas. Mice are not readily susceptible to infection by Leishmania (Viannia) spp., but cutaneous infection of hamsters with L. (V.) panamensis or L. (V.) guyanensis resulted in chronic lesions typical of the human disease caused by these parasites. Strikingly, infection of male hamsters resulted in significantly greater lesion size and severity, an increased rate of dissemination to distant cutaneous sites, and a greater parasite burden in the draining lymph node than infection in female animals. Two lines of evidence indicated this gender-related difference in disease evolution was determined at least in part by the sex hormone status of the animal. First, prepubertal male animals had smaller and/or less severe cutaneous lesions than adult male animals. Second, infection of testosterone-treated female animals resulted in significantly larger lesions than in untreated female animals. The increased severity of disease in male compared to female animals was associated with significantly greater intralesional expression of interleukin-4 (IL-4) (P = 0.04), IL-10 (P = 0.04), and transforming growth factor β (TGF-β) (P < 0.001), cytokines known to promote disease in experimental leishmaniasis. There was a direct correlation between the expression of TGF-β mRNA and lesion size (Spearman's correlation coefficient = 0.873; P < 0.001). These findings demonstrate an inherent risk of increased disease severity in male animals, which is associated with a more permissive immune response.

scholarly journals Gamma Interferon Produced by Antigen-Specific CD4+ T Cells Regulates the Mucosal Immune Responses to Citrobacter rodentium Infection

2010 ◽  
Vol 78 (6) ◽  
pp. 2653-2666 ◽  
Author(s):  
Hideyuki Shiomi ◽  
Atsuhiro Masuda ◽  
Shin Nishiumi ◽  
Masayuki Nishida ◽  
Tetsuya Takagawa ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Gamma Interferon ◽  
Immune Defense ◽  
Interleukin 4 ◽  
Mucosal Inflammation ◽  
Citrobacter Rodentium ◽  
Macrophage Phagocytosis ◽  
Ifn Γ ◽  
Deficient Mice

ABSTRACT Citrobacter rodentium, a murine model pathogen for enteropathogenic Escherichia coli, colonizes the surface of intestinal epithelial cells and causes mucosal inflammation. This bacterium is an ideal model for investigating pathogen-host immune interactions in the gut. It is well known that gene transcripts for Th1 cytokines are highly induced in colonic tissue from mice infected with C. rodentium. However, it remains to be seen whether the Th1 or Th2 cytokines produced by antigen-specific CD4+ T cells provide effective regulation of the host immune defense against C. rodentium infection. To investigate the antigen-specific immune responses, C. rodentium expressing ovalbumin (OVA-C. rodentium), a model antigen, was generated and used to define antigen-specific responses under gamma interferon (IFN-γ)-deficient or interleukin-4 (IL-4)-deficient conditions in vivo. The activation of antigen-specific CD4+ T cells and macrophage phagocytosis were evaluated in the presence of IFN-γ or IL-4 in vitro. IFN-γ-deficient mice exhibited a loss of body weight and a higher bacterial concentration in feces during OVA-C. rodentium infection than C57BL/6 (wild type) or IL-4-deficient mice. This occurred through the decreased efficiency of macrophage phagocytosis and the activation of antigen-specific CD4+ T cells. Furthermore, a deficiency in antigen-specific CD4+ T-cell-expressed IFN-γ led to a higher susceptibility to mucosal and gut-derived systemic OVA-C. rodentium infection. These results show that the IFN-γ produced by antigen-specific CD4+ T cells plays an important role in the defense against C. rodentium.

scholarly journals Interleukin-4 Receptor–Stat6 Signaling in Murine Infections with a Tissue-Dwelling Nematode Parasite

2001 ◽  
Vol 69 (12) ◽  
pp. 7743-7752 ◽  
Author(s):  
L. Spencer ◽  
L. Shultz ◽  
T. V. Rajan
Keyword(s):  
Immunoglobulin E ◽  
Inbred Mice ◽  
Secondary Infection ◽  
Critical Role ◽  
Gastrointestinal Nematode ◽  
Parasite Clearance ◽  
Epidemiological Studies ◽  
Interleukin 4 ◽  
Target Cells ◽  
Host Protection

ABSTRACT Interleukin-4 (IL-4) has been shown to be crucial in parasite expulsion in several gastrointestinal nematode infection models. Data from both epidemiological studies with humans and experimental infections in animals imply a critical role for the type II helper response, dominated by IL-4, in host protection. Here we utilized inbred mice on two distinct backgrounds to document the involvement of IL-4 in the clearance of a primary infection of Brugiafrom the murine host. Our data from infections of IL-4 receptor−/− and Stat6−/− mice further indicate that IL-4 exerts its effects by activating the Stat6 molecule in host target cells, a finding which links clearance requirements of a gastrointestinal tract-dwelling nematode with those of a tissue-dwelling nematode. Additionally, we show that the requirements for IL-4 receptor binding and Stat6 activation extend to accelerated clearance of a secondary infection as well. The data shown here, including analysis of cell populations at the site of infection and infection of immunoglobulin E (IgE)−/− mice, lead us to suggest that deficiencies in eosinophil recruitment and isotype switching to IgE production may be at least partially responsible for slower parasite clearance in the absence of IL-4.

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