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Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils.

ABSTRACT: Immunoglobulin D (IgD) is an enigmatic antibody isotype that mature B cells express together with IgM through alternative RNA splicing. Here we report active T cell-dependent and T cell-independent IgM-to-IgD class switching in B cells of the human upper respiratory mucosa. This process required activation-induced cytidine deaminase (AID) and generated local and circulating IgD-producing plasmablasts reactive to respiratory bacteria. Circulating IgD bound to basophils through a calcium-mobilizing receptor that induced antimicrobial, opsonizing, inflammatory and B cell-stimulating factors, including cathelicidin, interleukin 1 (IL-1), IL-4 and B cell-activating factor (BAFF), after IgD crosslinking. By showing dysregulation of IgD class-switched B cells and 'IgD-armed' basophils in autoinflammatory syndromes with periodic fever, our data indicate that IgD orchestrates an ancestral surveillance system at the interface between immunity and inflammation.

SUBMITTER: Chen K

PROVIDER: S-EPMC2785232 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils.

Chen Kang K Xu Weifeng W Wilson Melanie M He Bing B Miller Norman W NW Bengtén Eva E Edholm Eva-Stina ES Santini Paul A PA Rath Poonam P Chiu April A Cattalini Marco M Litzman Jiri J B Bussel James J Huang Bihui B Meini Antonella A Riesbeck Kristian K Cunningham-Rundles Charlotte C Plebani Alessandro A Cerutti Andrea A

Nature immunology 20090628 8

Immunoglobulin D (IgD) is an enigmatic antibody isotype that mature B cells express together with IgM through alternative RNA splicing. Here we report active T cell-dependent and T cell-independent IgM-to-IgD class switching in B cells of the human upper respiratory mucosa. This process required activation-induced cytidine deaminase (AID) and generated local and circulating IgD-producing plasmablasts reactive to respiratory bacteria. Circulating IgD bound to basophils through a calcium-mobilizin ...[more]

PMID: 19561614

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Project description:Introduction: Antimicrobial resistance (AMR) is a current global health threat and a challenge to the treatment of infectious diseases. The WHO advocates a strategy of antibiotic stewardship programs (ASP) in optimizing antimicrobial use in hospitals. This study aimed at assessing the existence of AMR surveillance and ASP implementation in health facilities in Tanzania in the year following the launch of the National Action Plan (NAP). Methodology: From December 2017 through July 2018, a descriptive cross-sectional study was conducted using a structured questionnaire administered online. A total of 199 health facilities in Tanzania mainland whose contacts was obtained from the Ministry of Health Community Development Gender Elderly and Children (MoHCDGEC) were reached by phone and thereafter, a survey was sent via text or e-mail to focal persons in the corresponding facilities. Results: Only 39 (32.5%) responses from contacted facilities were received and analyzed. Thirty (76.9%) of the facilities were government-owned. Of the 39 respondents surveyed, 13 (35.9%) declared to have implemented some sort of coordinated ASP to promote the rational use of antimicrobials at their facilities. The respondents reported the presence of guidelines for the implementation of ASP at variable proportions, whereas the presence of a committee for Infection Prevention and Control was reported by 27 (69.2%). Twenty-four (61.5%) had a Medical and Therapeutic Committee. Although all 39 (100%) respondents were aware of the presence of AMR in Tanzania, only 26 (66.7%) were aware of the presence of the Tanzanian NAP for AMR. Hospital antibiotic policy document was present in 6 (15.4%) facilities. Only 7 (17.9%) facilities conducted prescription auditing; 9 (23.1%) had a hospital formulary; 14 (35.9%) had standard hospital prescription. 9 (23.1%) had software for data storage about AMR. Only 7 (17.9%) facilities conducted microorganisms' susceptibility tests and kept the record of the microorganism susceptibility testing. Conclusion: Our study found the existence of AMR surveillance activities and ASP implementation in Tanzania, albeit at a low level. The implementation was inconsistent across the surveyed facilities. These data have identified areas of improvement in addressing AMR in Tanzania through the NAP.

Project description:Rationale: Pulmonary hypertension (PH) is a life-threatening cardiopulmonary disorder in which inflammation and immunity have emerged as critical early pathogenic elements. Although proinflammatory processes in PH and pulmonary arterial hypertension (PAH) are the focus of extensive investigation, the initiating mechanisms remain elusive.Objectives: We tested whether activation of the complement cascade is critical in regulating proinflammatory and pro-proliferative processes in the initiation of experimental hypoxic PH and can serve as a prognostic biomarker of outcome in human PAH.Methods: We used immunostaining of lung tissues from experimental PH models and patients with PAH, analyses of genetic murine models lacking specific complement components or circulating immunoglobulins, cultured human pulmonary adventitial fibroblasts, and network medicine analysis of a biomarker risk panel from plasma of patients with PAH.Measurements and Main Results: Pulmonary perivascular-specific activation of the complement cascade was identified as a consistent critical determinant of PH and PAH in experimental animal models and humans. In experimental hypoxic PH, proinflammatory and pro-proliferative responses were dependent on complement (alternative pathway and component 5), and immunoglobulins, particularly IgG, were critical for activation of the complement cascade. We identified Csf2/GM-CSF as a primary complement-dependent inflammatory mediator. Furthermore, using network medicine analysis of a biomarker risk panel from plasma of patients with PAH, we demonstrated that complement signaling can serve as a prognostic factor for clinical outcome in PAH.Conclusions: This study establishes immunoglobulin-driven dysregulated complement activation as a critical pathobiological mechanism regulating proinflammatory and pro-proliferative processes in the initiation of experimental hypoxic PH and demonstrates complement signaling as a critical determinant of clinical outcome in PAH.

Dataset Information

Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils.

Publications

Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils.

Similar Datasets

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