scholarly journals Assembly of a spatial circuit of T-bet–expressing T and B lymphocytes is required for antiviral humoral immunity

2021 ◽  
Vol 6 (60) ◽  
pp. eabi4710
Author(s):  
Alejandra Mendoza ◽  
William T. Yewdell ◽  
Beatrice Hoyos ◽  
Michail Schizas ◽  
Regina Bou-Puerto ◽  
...  
Keyword(s):  
B Lymphocytes ◽  
Inflammatory Responses ◽  
Influenza Infection ◽  
Humoral Response ◽  
Antiviral Immunity ◽  
T And B Lymphocytes ◽  
Class Switching ◽  
Draining Lymph Node ◽  
Ifn Γ

Effective antiviral immunity requires generation of T and B lymphocytes expressing the transcription factor T-bet, a regulator of type 1 inflammatory responses. Using T-bet expression as an endogenous marker for cells participating in a type 1 response, we report coordinated interactions of T-bet–expressing T and B lymphocytes on the basis of their dynamic colocalization at the T cell zone and B follicle boundary (T-B boundary) and germinal centers (GCs) during lung influenza infection. We demonstrate that the assembly of this circuit takes place in distinct anatomical niches within the draining lymph node, guided by CXCR3 that enables positioning of TH1 cells at the T-B boundary. The encounter of B and TH1 cells at the T-B boundary enables IFN-γ produced by the latter to induce IgG2c class switching. Within GCs, T-bet+ TFH cells represent a specialized stable sublineage required for GC growth but dispensable for IgG2c class switching. Our studies show that during respiratory viral infection, T-bet–expressing T and B lymphocytes form a circuit assembled in a spatiotemporally controlled manner that acts as a functional unit enabling a robust and coherent humoral response tailored for optimal antiviral immunity.

scholarly journals Trichinella spiralis reinfection: changes in cellular and humoral immune response in BALB/c mice

2012 ◽  
Vol 49 (4) ◽  
pp. 201-210 ◽  
Author(s):  
E. Dvorožňáková ◽  
M. Kołodziej-Sobocińska ◽  
Z. Hurníková
Keyword(s):  
Immune Response ◽  
B Lymphocytes ◽  
Trichinella Spiralis ◽  
Parasite Burden ◽  
Humoral Response ◽  
T And B Lymphocytes ◽  
High Concentration ◽  
Immunological Parameters ◽  
Humoral Immune ◽  
Ifn Γ

AbstractTrichinella spiralis infection induces a host cell-mediated and humoral response. The role of T and B lymphocytes in the immune response of mice reinfected with 2 × 400 T. spiralis larvae was studied in relation to the parasite burden. BALB/c mice were infected on days 0 and 60 and immunological parameters were examined within a period of 180 days. In comparison with a single T. spiralis infection, T- and B-lymphocytes in reinfected mice responded by a significant increase in the proliferative activity during 10 days after reinfection. At the same time, the percentages of CD4+ T-cells of reinfected mice were also increased. In contrast, the CD8+ T-cell numbers were significantly reduced almost 30 days after reinfection. High concentration of serum IFN-γ lasted till the end of the experiment. The IL-5 level was increased only for 2 weeks after reinfection, followed by its decrease. Kinetics of specific anti-Trichinella immunoglobulins IgG2a was not affected with reinfection, but specific antibodies IgG1 significantly increased after reinfection and persisted elevated till the end of the experiment. Lower numbers of adults (69.2 % reduction) in the small intestine and 72.3 % reduction in muscle larvae were found after reinfection. Stimulation of the host immune response — the increased activity of CD4+ T lymphocytes and high levels of IFN-γ and specific IgG1 after reinfection, contributed to the reduction of the parasite burden.

scholarly journals Transcriptional Profiling of Mouse Eosinophils Identifies Distinct Gene Signatures Following Cellular Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Avishay Dolitzky ◽  
Guy Shapira ◽  
Sharon Grisaru-Tal ◽  
Inbal Hazut ◽  
Shmulik Avlas ◽  
...  
Keyword(s):  
Cell Surface ◽  
Inflammatory Responses ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Bioinformatics Analyses ◽  
E Coli ◽  
Ifn Γ ◽  
Transcriptome Signature

Eosinophils are multifunctional, evolutionary conserved leukocytes that are involved in a plethora of responses ranging from regulation of tissue homeostasis to host defense and cancer. Eosinophils have been studied mostly in the context of Type 2 inflammatory responses such as those found in allergy. Nonetheless, it is now evident that they participate in Type 1 inflammatory responses and can respond to Type 1 cytokines such as IFN-γ. Recent data suggest that the pleotropic roles of eosinophils are due to heterogeneous responses to environmental cues. Despite this, the activation profile of eosinophils, in response to various stimuli is yet to be defined. To better understand the transcriptional spectrum of eosinophil activation, we exposed eosinophils to Type 1 (e.g. IFN-γ, E. coli) vs. Type 2 (e.g. IL-4) conditions and subjected them to global RNA sequencing. Our analyses show that IL-4, IFN-γ, E. coli and IFN-γ in the presence of E. coli (IFN-γ/E. coli)-stimulated eosinophils acquire distinct transcriptional profiles, which polarize them towards what we termed Type 1 and Type 2 eosinophils. Bioinformatics analyses using Gene Ontology based on biological processes revealed that different stimuli induced distinct pathways in eosinophils. These pathways were confirmed using functional assays by assessing cytokine/chemokine release (i.e. CXCL9, CCL24, TNF-α and IL-6) from eosinophils following activation. In addition, analysis of cell surface markers highlighted CD101 and CD274 as potential cell surface markers that distinguish between Type 1 and Type 2 eosinophils, respectively. Finally, the transcriptome signature of Type 1 eosinophils resembled that of eosinophils that were obtained from mice with experimental colitis whereas the transcriptome signature of Type 2 eosinophils resembled that of eosinophils from experimental asthma. Our data demonstrate that eosinophils are polarized to distinct “Type 1” and “Type 2” phenotypes following distinct stimulations. These findings provide fundamental knowledge regarding the heterogeneity of eosinophils and support the presence of transcriptional differences between Type 1 and Type 2 cells that are likely reflected by their pleotropic activities in diverse disease settings.

scholarly journals Novel Role for Interleukin-17 in Enhancing Type 1 Helper T Cell Immunity in the Female Genital Tract following Mucosal Herpes Simplex Virus 2 Vaccination

2017 ◽  
Vol 91 (23) ◽  
Author(s):  
Puja Bagri ◽  
Varun C. Anipindi ◽  
Philip V. Nguyen ◽  
Danielle Vitali ◽  
Martin R. Stämpfli ◽  
...  
Keyword(s):  
T Cells ◽  
Genital Tract ◽  
Female Genital Tract ◽  
Antiviral Immunity ◽  
Cell Immunity ◽  
Ifn Γ ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2 ◽  
Female Genital

ABSTRACT It is well established that interferon gamma (IFN-γ) production by CD4+ T cells is critical for antiviral immunity against herpes simplex virus 2 (HSV-2) genital infection. However, the role of interleukin-17A (IL-17A) production by CD4+ T cells in HSV-2 antiviral immunity is yet to be elucidated. Here we demonstrate that IL-17A plays an important role in enhancing antiviral T helper type 1 (Th1) responses in the female genital tract (FGT) and is essential for effective protection conferred by HSV-2 vaccination. While IL-17A did not play a critical role during primary genital HSV-2 infection, seen by lack of differences in susceptibility between IL-17A-deficient (IL-17A −/−) and wild-type (WT) C57BL/6 mice, it was critical for mediating antiviral responses after challenge/reexposure. Compared to WT mice, IL-17A −/− mice (i) infected intravaginally and reexposed or (ii) vaccinated intranasally and challenged intravaginally demonstrated poor outcomes. Following intravaginal HSV-2 reexposure or challenge, vaccinated IL-17A −/− mice had significantly higher mortality, greater disease severity, higher viral shedding, and higher levels of proinflammatory cytokines and chemokines in vaginal secretions. Furthermore, IL-17A −/− mice had impaired Th1 cell responses after challenge/reexposure, with significantly lower proportions of vaginal IFN-γ+ CD4+ T cells. The impaired Th1 cell responses in IL-17A −/− mice coincided with smaller populations of IFN-γ+ CD4+ tissue resident memory T (TRM) cells in the genital tract postimmunization. Taken together, these findings describe a novel role for IL-17A in regulating antiviral IFN-γ+ Th1 cell immunity in the vaginal tract. This strategy could be exploited to enhance antiviral immunity following HSV-2 vaccination. IMPORTANCE T helper type 1 (Th1) immunity, specifically interferon gamma (IFN-γ) production by CD4+ T cells, is critical for protection against genital herpesvirus (HSV-2) infection, and enhancing this response can potentially help improve disease outcomes. Our study demonstrated that interleukin-17A (IL-17A) plays an essential role in enhancing antiviral Th1 responses in the female genital tract (FGT). We found that in the absence of IL-17A, preexposed and vaccinated mice showed poor disease outcomes and were unable to overcome HSV-2 reexposure/challenge. IL-17A-deficient mice (IL-17A −/−) had smaller populations of IFN-γ+ CD4+ tissue resident memory T (TRM) cells in the genital tract postimmunization than did wild-type (WT) mice, which coincided with attenuated Th1 responses postchallenge. This has important implications for developing effective vaccines against HSV-2, as we propose that strategies inducing IL-17A in the genital tract may promote more effective Th1 cell immunity and better overall protection.

Responses of inbred mouse strains to infection with intestinal nematodes

2003 ◽  
Vol 77 (2) ◽  
pp. 119-124 ◽  
Author(s):  
M.S. Dehlawi ◽  
P.K. Goyal
Keyword(s):  
Time Course ◽  
Inflammatory Responses ◽  
Trichinella Spiralis ◽  
Inbred Mice ◽  
Paneth Cell ◽  
High Responder ◽  
Mouse Strains ◽  
Ifn Γ

AbstractComparisons were made of the immune and inflammatory responses of four strains of inbred mice to infection with the intestinal nematodes Trichinella spiralis and Nippostrongylus brasiliensis to determine whether genetically determined ‘high responsiveness’ to infection, seen most clearly in intestinal responses, is independent of the parasite concerned and necessarily correlated with protection. The time course of infection was followed by counting adult worms at intervals after infection. Mucosal mast cells and Paneth cell numbers were determined as indices of the intestinal inflammatory response. Levels of IgG2a and IgG1 antibodies and of the cytokines IFN-γ and IL-5 released from in vitro-stimulated mesenteric node lymphocytes were measured to assess type 1 and type 2 responses. NIH and CBA mice were the most resistant to T. spiralis and N. brasiliensis respectively, resistance in each case being correlated with the most intense intestinal inflammatory responses. C57BL/10 (B10) and B10.BR were the least resistant to T. spiralis, but were as resistant as CBA to N. brasiliensis, despite their intestinal inflammatory responses to both parasites being much lower than the other two strains. Mice infected with T. spiralis made the expected switch from a type 1 (IFN-γ) to a type 2 (IL-5) response between days 2 and 8, and there were no significant differences in levels of these cytokines between the strains. In contrast, when infected with N. brasiliensis, CBA showed an IFN-γ response at day 4, all strains switching to IL-5 by day 8 and NIH mice releasing the greatest amount of IL-5. The results indicate that the ‘high responder’ phenotype to intestinal nematode infection is in part determined by host characteristics, but is also determined by the parasite concerned – seen most clearly by the differences between NIH and CBA when infected with T. spiralis and N. brasiliensis. The fact that ‘low responder’ B10 background mice were more resistant to N. brasiliensis than ‘high responder’ NIH implies that each parasite elicits a particular pattern of protective host responses, rather than parasites being differentially susceptible to the same response profile.

scholarly journals BCG and BCGΔBCG1419c protect type 2 diabetic mice against tuberculosis via different participation of T and B lymphocytes, dendritic cells and pro-inflammatory cytokines

npj Vaccines ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Cristian Alfredo Segura-Cerda ◽  
Brenda Marquina-Castillo ◽  
Vasti Lozano-Ordaz ◽  
Dulce Mata-Espinosa ◽  
Jorge Alberto Barrios-Payán ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
B Lymphocytes ◽  
Inflammatory Cytokines ◽  
B Lymphocyte ◽  
Acute Infection ◽  
T And B Lymphocytes ◽  
Middle Income ◽  
Ifn Γ ◽  
Pro Inflammatory Cytokines

Abstract Comorbidity between Tuberculosis (TB) and type 2 diabetes (T2D) is one of the greatest contributors to the spread of Mycobacterium tuberculosis (M. tuberculosis) in low- and middle-income countries. T2D compromises key steps of immune responses against M. tuberculosis and it might affect the protection afforded by vaccine candidates against TB. We compared the protection and immune response afforded by the BCGΔBCG1419c vaccine candidate versus that of wild-type BCG in mice with T2D. Vaccination with both BCGΔBCG1419c, BCG or infection with M. tuberculosis reduced weight loss, hyperglycemia, and insulin resistance during T2D progression, suggesting that metabolic changes affecting these parameters were affected by mycobacteria. For control of acute TB, and compared with non-vaccinated controls, BCG showed a dominant T CD4+ response whereas BCGΔBCG1419c showed a dominant T CD8+/B lymphocyte response. Moreover, BCG maintained an increased response in lung cells via IFN-γ, TNF-α, and IL-4, while BCGΔBCG1419c increased IFN-γ but reduced IL-4 production. As for chronic TB, and compared with non-vaccinated controls, both BCG strains had a predominant presence of T CD4+ lymphocytes. In counterpart, BCGΔBCG1419c led to increased presence of dendritic cells and an increased production of IL-1 β. Overall, while BCG effectively reduced pneumonia in acute infection, it failed to reduce it in chronic infection, whereas we hypothesize that increased production of IL-1 β induced by BCGΔBCG1419c contributed to reduced pneumonia and alveolitis in chronic TB. Our results show that BCG and BCGΔBCG1419c protect T2D mice against TB via different participation of T and B lymphocytes, dendritic cells, and pro-inflammatory cytokines.

Relationship among T- and B-lymphocytes of the peripheral blood and thyroid tissue in patients with Graves' disease

2019 ◽  
Author(s):  
Margarita A Dudina ◽  
Andrey A Savchenko ◽  
Sergey A Dogadin ◽  
Alexandr G Borisov ◽  
Igor V Kudryavcev ◽  
...  
Keyword(s):  
B Lymphocytes ◽  
Peripheral Blood ◽  
Thyroid Tissue ◽  
T And B Lymphocytes ◽  
Graves Disease

scholarly journals Transplantable progenitors of natural killer cells are distinct from those of T and B lymphocytes.

1986 ◽  
Vol 83 (10) ◽  
pp. 3427-3431 ◽  
Author(s):  
J. Hackett ◽  
G. C. Bosma ◽  
M. J. Bosma ◽  
M. Bennett ◽  
V. Kumar
Keyword(s):  
Natural Killer Cells ◽  
Natural Killer ◽  
B Lymphocytes ◽  
T And B Lymphocytes ◽  
Killer Cells

scholarly journals MBD2 acts as a repressor to maintain the homeostasis of the Th1 program in type 1 diabetes by regulating the STAT1-IFN-γ axis

2021 ◽  
Author(s):  
Tiantian Yue ◽  
Fei Sun ◽  
Faxi Wang ◽  
Chunliang Yang ◽  
Jiahui Luo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Type 1 Diabetes ◽  
Adoptive Transfer ◽  
Nod Mice ◽  
Transcriptional Level ◽  
Clinical Settings ◽  
Cpg Dna ◽  
Ifn Γ

AbstractThe methyl-CpG-binding domain 2 (MBD2) interprets DNA methylome-encoded information through binding to the methylated CpG DNA, by which it regulates target gene expression at the transcriptional level. Although derailed DNA methylation has long been recognized to trigger or promote autoimmune responses in type 1 diabetes (T1D), the exact role of MBD2 in T1D pathogenesis, however, remains poorly defined. Herein, we generated an Mbd2 knockout model in the NOD background and found that Mbd2 deficiency exacerbated the development of spontaneous T1D in NOD mice. Adoptive transfer of Mbd2−/− CD4 T cells into NOD.scid mice further confirmed the observation. Mechanistically, Th1 stimulation rendered the Stat1 promoter to undergo a DNA methylation turnover featured by the changes of DNA methylation levels or patterns along with the induction of MBD2 expression, which then bound to the methylated CpG DNA within the Stat1 promoter, by which MBD2 maintains the homeostasis of Th1 program to prevent autoimmunity. As a result, ectopic MBD2 expression alleviated CD4 T cell diabetogenicity following their adoptive transfer into NOD.scid mice. Collectively, our data suggest that MBD2 could be a viable target to develop epigenetic-based therapeutics against T1D in clinical settings.

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