Pivotal Advance: Eosinophils mediate early alum adjuvant-elicited B cell priming and IgM production

Wang, H.-B.; Weller, Peter F.

doi:10.1189/jlb.0607392

Cited by 102 publications

(80 citation statements)

References 24 publications

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“…The results indicate that innate immune cells such as eosinophils triggered by TCS contribute to the initial IL-4 production, thus playing a critical role in initiating the Th2-type response, in favoring B cell priming and in recruiting Th2 cells to lungs as reported recently [31,40]. Our observations are consistent with the results of Jordan et al [39] and Wang et al [41]. Jordan et al found that injection of mice with alum led to the priming of spleen B cells and to the accumulation of a population of IL-4-producing Gr-1 + cells in the spleen.…”

Section: Discussionsupporting

confidence: 93%

Trichosanthin functions as Th2-type adjuvant in induction of allergic airway inflammation

et al. 2009

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It is important to understand the pathogenesis of asthma induced by natural allergens, which could exclude the interference of artificial adjuvant and provide insights of natural immune response in the disease. In the present study, we show that Trichosanthin (TCS) could induce airway inflammation even without the help of alum. Furthermore, TCS appeared capable of replacing alum to promote OVA-specific airway inflammation. TCS induced accumulation of IL-4-producing eosinophils in peritoneum at an early stage and the adjuvant function of TCS was eliminated by blockage of IL-4 at this stage. Finally, the eosinophils triggered by TCS from WT mice, but not from IL-4-deficient mice were shown to function as adjuvant for the induction of OVA-specific Th2 responses. Our data indicate that TCS is not only an allergen, but also a Th2-type adjuvant modulating the switching of immune responses to a Th2 pathway. This chain of events results from IL-4 production by eosinophils at an early stage of TCS-priming. In conclusion, TCS may be useful as a Th2 adjuvant, and innate immune cells, such as eosinophils, may be a good target to study the initiation of Th2 response.

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Section: Discussionsupporting

confidence: 93%

Trichosanthin functions as Th2-type adjuvant in induction of allergic airway inflammation

et al. 2009

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“…They do this, at least in part, by synthesizing and secreting a surprisingly broad spectrum of different cytokines and immune mediators [2]. In immune responses, activated eosinophils show an enhanced expression of cytokines [7][8][9]. Although activation can be induced by adjuvants alone, a stable activation is achieved only in antigen-induced immune responses.…”

Section: Introductionmentioning

confidence: 99%

“…In particular, the precipitation of antigen with aluminum hydroxide (alum) has an enhancing effect on the immune response, and alum administration has been shown to stimulate eosinophil development in the bone marrow and to promote their accumulation in the spleen [9]. In T cell-dependent immune responses, B cell activation can result in an immediate extrafollicular response to antigenic challenge, whereby antigen-activated B cells differentiate rapidly into IgM-secreting plasma cells.…”

Section: Introductionmentioning

confidence: 99%

“…In T cell-dependent immune responses, B cell activation can result in an immediate extrafollicular response to antigenic challenge, whereby antigen-activated B cells differentiate rapidly into IgM-secreting plasma cells. This early immediate B cell response to antigenic challenge requires the presence of eosinophils [8,9], whereas the induction of splenic germinal centres (GC) and the generation of high-affinity IgG-secreting plasma cells seem to be independent of them [25].…”

Section: Introductionmentioning

confidence: 99%

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Eosinophils: important players in humoral immunity

Berek

2015

Clinical and Experimental Immunology

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Summary Eosinophils perform numerous tasks. They are involved in inflammatory reactions associated with innate immune defence against parasitic infections and are also involved in pathological processes in response to allergens. Recently, however, it has become clear that eosinophils also play crucial non‐inflammatory roles in the generation and maintenance of adaptive immune responses. Eosinophils, being a major source of the plasma cell survival factor APRIL (activation and proliferation‐induced ligand), are essential not only for the long‐term survival of plasma cells in the bone marrow, but also for the maintenance of these cells in the lamina propria which underlies the gut epithelium. At steady state under non‐inflammatory conditions eosinophils are resident cells of the gastrointestinal tract, although only few are present in the major organized lymphoid tissue of the gut – the Peyer's patches (PP). Surprisingly, however, lack of eosinophils abolishes efficient class‐switching of B cells to immunoglobulin (Ig)A in the germinal centres of PP. Thus, eosinophils are required to generate and to maintain mucosal IgA plasma cells, and as a consequence their absence leads to a marked reduction of IgA both in serum and in the gut‐associated lymphoid tissues (GALT). Eosinophils thus have an essential part in long‐term humoral immune protection, as they are crucial for the longevity of antibody‐producing plasma cells in the bone marrow and, in addition, for gut immune homeostasis.

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“…It also elicits and activates Il-4 expressing eosinophils that prime B cell responses to generate antigen-specific IgM [188]. Dysphagia (difficulty swallowing) is a common problem affecting up to 22% of patients in primary care [189], and a characteristic feature of Alzheimer's, Parkinson's and ALS.…”

Section: Asthma Dermatitis and Eosinophilic Esophagitismentioning

confidence: 99%

Aluminum?s Role in CNS-immune System Interactions leading to Neurological Disorders

CA¹

2013

Immunome Res

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Multisystem interactions are well established in neurological disorders, in spite of conventional views that only the central nervous system (CNS) is impacted. We review evidence for mutual interactions between the immune and nervous systems and show how these seem to be implicated in the origin and progression of nervous system disorders. Well-established immune system triggers leading to autoimmune reactions are considered. Of these, aluminum, a known neurotoxicant, may be of particular importance. We have demonstrated elsewhere that aluminum has the potential to induce damage at a range of levels in the CNS leading to neuronal death, circuit malfunction and ultimately, system failure. Aluminum is widely used as an adjuvant in various vaccine formulations and has been implicated in a multisystem disorder termed "autoimmune/inflammatory syndrome induced by adjuvants" (ASIA). The implications of aluminum-induced ASIA in some disorders of the CNS are considered. We propose a unified theory capturing a progression from a local response to a systemic response initiated by disruption of water-based interfaces of exposed cells.

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Pivotal Advance: Eosinophils mediate early alum adjuvant-elicited B cell priming and IgM production

Cited by 102 publications

References 24 publications

Trichosanthin functions as Th2-type adjuvant in induction of allergic airway inflammation

Trichosanthin functions as Th2-type adjuvant in induction of allergic airway inflammation

Eosinophils: important players in humoral immunity

Aluminum?s Role in CNS-immune System Interactions leading to Neurological Disorders

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