Mycobacterium tuberculosis promotes Th17 expansion via regulation of human dendritic cells toward a high CD14 and low IL-12p70 phenotype that reprograms upon exogenous IFN-{gamma}
The capacity to develop protective immunity against mycobacteria is heterogeneously distributed among human beings, and it is currently unknown why the initial immune response induced against Mycobacterium tuberculosis (Mtb) does not provide proper clearance of this pathogen. Dendritic cells (DCs) are some of the first cells to interact with Mtb and they play an essential role in development of protective immunity against Mtb. Given that Mtb-infected macrophages have difficulties in degrading Mtb, they need help from IFN--producing CD4+ T cells propagated via IL-12p70-producing DCs. Here we report that Mtb modifies human D...
Source: International Immunology - November 21, 2014 Category: Allergy & Immunology Authors: Sondergaard, J. N., Laursen, J. M., Rosholm, L. B., Brix, S. Tags: Original Research Source Type: research
Responses of macrophages to the danger signals released from necrotic cells
In this study, we focused on the expression of chemokines by macrophages stimulated with necrotic cells. In mouse bone-marrow-derived macrophages, the chemokine monocyte chemoattractant protein (MCP)-3 was induced at both the mRNA and protein levels in response to heat-killed murine cells. The induction of MCP-3 was also observed in MyD88-deficient macrophages, indicating that Toll-like receptors and the IL-1 receptor are not involved in this response. Consistent with this observation, the activation of NF-B was not detected in RAW264.7 macrophages stimulated with necrotic cells. Treatments with proteinase K, DNaseI or RNa...
Source: International Immunology - November 21, 2014 Category: Allergy & Immunology Authors: Kimura, T., Kobayashi, S., Hanihara-Tatsuzawa, F., Sayama, A., MaruYama, T., Muta, T. Tags: featured content Source Type: research
ERAP1 functions override the intrinsic selection of specific antigens as immunodominant peptides, thereby altering the potency of antigen-specific cytolytic and effector memory T-cell responses
Endoplasmic reticulum aminopeptidase 1 (ERAP1) is a critical component of the adaptive immune system that has been shown to increase or decrease the presentation of specific peptides on MHC class I molecules. Here, we have demonstrated that ERAP1 functions are not only important during the presentation of antigen-derived peptides, but these functions can also completely change which antigen-derived peptides ultimately become selected as immunodominant T-cell epitopes. Our results suggest that ERAP1 may do this by destroying epitopes that would otherwise become immunodominant in the absence of adequate ERAP1 functionality. ...
Source: International Immunology - November 21, 2014 Category: Allergy & Immunology Authors: Rastall, D. P. W., Aldhamen, Y. A., Seregin, S. S., Godbehere, S., Amalfitano, A. Tags: Original Research Source Type: research
Indoleamine 2,3-dioxygenase increases p53 levels in alloreactive human T cells, and both indoleamine 2,3-dioxygenase and p53 suppress glucose uptake, glycolysis and proliferation
In conclusion, in alloreactive T cells, IDO increases p53 levels, and both IDO and p53 inhibit cell proliferation, glucose consumption and glycolysis. Lactate production and glutaminolysis are also suppressed by IDO, but not by p53. (Source: International Immunology)
Source: International Immunology - November 21, 2014 Category: Allergy & Immunology Authors: Eleftheriadis, T., Pissas, G., Antoniadi, G., Spanoulis, A., Liakopoulos, V., Stefanidis, I. Tags: Original Research Source Type: research
Enhanced auto-antibody production and Mott cell formation in Fc{mu}R-deficient autoimmune mice
The IgM-Fc receptor (FcμR) is involved in IgM homeostasis as evidenced by increased pre-immune serum IgM and natural auto-antibodies of both IgM and IgG isotypes in Fcmr-deficient C57BL/6 (B6) mice. To determine the impact of Fcmr-ablation on autoimmunity, we introduced the Fcmr null mutation onto the Fas-deficient autoimmune-prone B6.MRL Fas lpr/lpr mouse background (B6/lpr). Both IgM and IgG auto-antibodies against dsDNA or chromatin appeared earlier in FcμR(–) B6/lpr than FcμR(+) B6/lpr mice, but this difference became less pronounced with age. Splenic B2 cells, which were 2-fold elevated in FcμR(...
Source: International Immunology - November 21, 2014 Category: Allergy & Immunology Authors: Honjo, K., Kubagawa, Y., Suzuki, Y., Takagi, M., Ohno, H., Bucy, R. P., Izui, S., Kubagawa, H. Tags: Original Research Source Type: research
The role of phage display in therapeutic antibody discovery
Phage display involves the expression of selected proteins on the surface of filamentous phage through fusion with phage coat protein, with the genetic sequence packaged within, linking phenotype to genotype selection. When combined with antibody libraries, phage display allows for rapid in vitro selection of antigen-specific antibodies and recovery of their corresponding coding sequence. Large non-immune and synthetic human libraries have been constructed as well as smaller immune libraries based on capturing a single individual’s immune repertoire. This completely in vitro process allows for isolation of antibodies...
Source: International Immunology - November 21, 2014 Category: Allergy & Immunology Authors: Chan, C. E. Z., Lim, A. P. C., MacAry, P. A., Hanson, B. J. Tags: Invited review Source Type: research
In This Issue
(Source: International Immunology)
Source: International Immunology - November 21, 2014 Category: Allergy & Immunology Tags: In This Issue Source Type: research
Table of Contents
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Source: International Immunology - November 21, 2014 Category: Allergy & Immunology Tags: Cover / Standing Material Source Type: research
Subscriptions
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Source: International Immunology - November 21, 2014 Category: Allergy & Immunology Tags: Cover / Standing Material Source Type: research
Cover
(Source: International Immunology)
Source: International Immunology - November 21, 2014 Category: Allergy & Immunology Tags: Cover / Standing Material Source Type: research
Cathelicidin rCRAMP stimulates rat mast cells to generate cysteinyl leukotrienes, synthesize TNF and migrate: involvement of PLC/A2, PI3K and MAPK signaling pathways
Cathelicidins represent a family of cationic peptides involved in host defense systems. Apart from exerting direct anti-microbial effects, cathelicidins can regulate immune responses by affecting the activity of cells playing a role in antibacterial defense. Taking into account that mast cells are critical components of host defense, the aim of this study was to determine whether rat cathelicidin-related anti-microbial peptide (rCRAMP) can influence mast cell activity. We have demonstrated that activation of fully mature rat mast cells with rCRAMP resulted in generation and release of cysteinyl leukotrienes (cysLTs). Howev...
Source: International Immunology - October 18, 2014 Category: Allergy & Immunology Authors: Bąbolewska, E., Pietrzak, A., Brzeziłska-Błaszczyk, E. Tags: Original Research Source Type: research
Leptin deficiency in vivo enhances the ability of splenic dendritic cells to activate T cells
Leptin is a pleiotropic adipokine that is critical for regulating food intake and energy expenditure and also participates in functions of the immune system, including those of antigen-presenting cells. Here, we assess the effect of leptin deficiency on the function splenic dendritic cells (sDC). sDC from leptin-deficient mice (Lepob) were evaluated ex vivo for phenotype, ability to respond to inflammatory stimuli, to acquire and process antigens and to activate T cells. The data show that Lepob sDC express activation markers similar to controls and respond similarly to LPS activation or anti-CD40 cross-linking. In additio...
Source: International Immunology - October 18, 2014 Category: Allergy & Immunology Authors: Ramirez, O., Garza, K. M. Tags: Original Research Source Type: research
A novel mucosal vaccine targeting Peyer's patch M cells induces protective antigen-specific IgA responses
Mucosal vaccines can induce mucosal immunity, including antigen-specific secretory IgA production, to protect from invasion by pathogens and to neutralize toxins at mucosal surfaces. We established an effective antigen-delivering fusion protein, anti-GP2-SA, as a mucosal vaccine. The anti-GP2-SA consists of streptavidin (SA) fused to the antigen-binding fragment region from a mAb against glycoprotein 2 (GP2), an antigen-uptake receptor specifically expressed on M cells. Anti-GP2-SA targets antigen-sampling M cells in the follicle-associated epithelium covering Peyer’s patches. Immunofluorescence showed that anti-GP2-...
Source: International Immunology - October 18, 2014 Category: Allergy & Immunology Authors: Shima, H., Watanabe, T., Fukuda, S., Fukuoka, S.-I., Ohara, O., Ohno, H. Tags: featured content Source Type: research
NF-{kappa}B RELA-deficient bone marrow macrophages fail to support bone formation and to maintain the hematopoietic niche after lethal irradiation and stem cell transplantation
Bone remodeling and hematopoiesis are interrelated and bone marrow (BM) macrophages are considered to be important for both bone remodeling and maintenance of the hematopoietic niche. We found that NF-B Rela-deficient chimeric mice, generated by transplanting Rela –/– fetal liver cells into lethally irradiated hosts, developed severe osteopenia, reduced lymphopoiesis and enhanced mobilization of hematopoietic stem and progenitor cells when BM cells were completely substituted by Rela-deficient cells. Rela –/– hematopoietic stem cells from fetal liver had normal hematopoietic ability, but those har...
Source: International Immunology - October 18, 2014 Category: Allergy & Immunology Authors: Mise-Omata, S., Alles, N., Fukazawa, T., Aoki, K., Ohya, K., Jimi, E., Obata, Y., Doi, T. Tags: Original Research Source Type: research
NKG2D functions as an activating receptor on natural killer cells in the common marmoset (Callithrix jacchus)
The natural killer group 2 membrane D (NKG2D) receptor is an NK-activating receptor that plays an important role in host defense against tumors and viral infections. Although the marmoset is an important and reliable animal model, especially for the study of human-specific viral infections, functional characterization of NKG2D on marmoset NK cells has not previously been conducted. In the present study, we investigated a subpopulation of marmoset NK cells that express NKG2D and exhibit cytolytic potential. On the basis of their CD16 and CD56 expression patterns, marmoset NK cells can be classified into three subpopulations...
Source: International Immunology - October 18, 2014 Category: Allergy & Immunology Authors: Watanabe, M., Kudo, Y., Kawano, M., Nakayama, M., Nakamura, K., Kameda, M., Ebara, M., Sato, T., Nakamura, M., Omine, K., Kametani, Y., Suzuki, R., Ogasawara, K. Tags: Original Research Source Type: research
