Ex Vivo Immunomodulatory Effects of Lactobacillus-, Lacticaseibacillus-, and Bifidobacterium-Containing Synbiotics on Human Peripheral Blood Mononuclear Cells and Monocyte-Derived Dendritic Cells in the Context of Grass Pollen Allergy

Alexander Heldner,Matthew D Heath,Benjamin Schnautz,Sebastian Kotz,Adam Chaker,Matthias F Kramer,Constanze A Jakwerth,Ulrich M Zissler,Carsten B Schmidt-Weber,Simon Blank

doi:10.1007/s12602-022-09920-w

Abstract

Sensing of the intestinal microbiota by the host immune system is important to induce protective immune responses. Hence, modification of the gut microbiota might be able to prevent or treat allergies, mediated by proinflammatory Th2 immune responses. The aim was to investigate the ex vivo immunomodulatory effects of the synbiotics Pollagen® and Kallergen®, containing the probiotic bacterial strains Lactobacillus, Lacticaseibacillus and Bifidobacterium, in the context of grass pollen allergy. Peripheral blood mononuclear cells (PBMCs) from grass pollen–allergic patients and healthy controls were stimulated with grass pollen extract (GPE) and synbiotics and Gata3 expression and cytokine secretion analyzed. Monocyte-derived dendritic cells (MoDCs) cells were matured in the presence of GPE and synbiotics, co-cultured with autologous naïve T cells and maturation markers and cytokine secretion analyzed. GPE stimulation of PBMCs from grass pollen–allergic patients resulted in a significant higher production of the Th2 cytokines IL-4, IL-5, IL-9 and IL-13 compared to healthy controls. Gata3+CD4+ T cell induction was independent of the allergic status. The synbiotics promoted IL-10 and IFN-γ secretion and downregulated the GPE-induced Th2-like phenotype. Co-culturing naïve T cells with MoDCs, matured in the presence of GPE and synbiotics, shifted the GPE-induced Th2 cytokine release towards Th1-Th17-promoting conditions in allergic subjects. The investigated synbiotics are effective in downregulating the GPE-induced Th2 immune response in PBMCs from grass pollen–allergic patients as well as in autologous MoDC-T cell stimulation assays. In addition to increased IL-10 release, the data indicates a shift from a Th2- to a more Th1- and Th17-like phenotype.

Highlights

Respiratory allergies to airborne allergen sources like pollen are the most frequent type-1 hypersensitivities
Different concentrations of the bacteria and different volumes of the supernatants were applied to grass pollen extract (GPE)-stimulated Peripheral blood mononuclear cells (PBMCs), and the volumes with the strongest inhibitory capacity on Gata3 expression while maintaining cell proliferation and viability were selected for further experiments
Stimulation of PBMCs from allergic patients with GPE resulted in a significant production of the Th2 cytokines IL-4, IL-5, IL-9, and IL-13

Summary

Introduction

Respiratory allergies to airborne allergen sources like pollen are the most frequent type-1 hypersensitivities. Sensitization rates to grass (Pooideae) pollen such as timothy grass (Phleum pretense) substantially increased over the last decades and nowadays range between 10 to 30% in the general population [1]. Pollen-monitoring networks were implemented in the last few years [2], avoidance of exposure to airborne allergens is nearly impossible. Allergen-specific immunotherapy (AIT) is the only curative treatment that is able to improve allergy-driven symptoms by inducing allergen-specific immune tolerance. Within the last few years novel therapeutic and preventive approaches were investigated.

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