Lipoteichoic Acid from Lacticaseibacillus rhamnosus GG Modulates Dendritic Cells and T Cells in the Gut

Adrián D Friedrich,Juliana Leoni,Daniel H González Maglio,Mariela L Paz

doi:10.3390/nu14030723

Abstract

Lipoteichoic acid (LTA) from Gram-positive bacteria exerts different immune effects depending on the bacterial source from which it is isolated. Lacticaseibacillus rhamnosus GG LTA (LGG-LTA) oral administration reduces UVB-induced immunosuppression and skin tumor development in mice. In the present work, we evaluate the immunomodulatory effect exerted by LGG-LTA in dendritic cells (DC) and T cells, both in vitro and in the gut-associated lymphoid tissue (GALT). During cell culture, LTA-stimulated BMDC increased CD86 and MHC-II expression and secreted low levels of pro and anti-inflammatory cytokines. Moreover, LTA-treated BMDC increased T cell priming capacity, promoting the secretion of IL-17A. On the other hand, in orally LTA-treated mice, a decrease in mature DC (lamina propria and Peyer’s patches) was observed. Concomitantly, an increase in IL-12p35 and IFN-γ transcription was presented (lamina propria and Peyer’s Patches). Finally, an increase in the number of CD103+ DC was observed in Peyer’s patches. Together, our data demonstrate that LGG-LTA activates DC and T cells. Moreover, we show that a Th1-biased immune response is triggered in vivo after oral LTA administration. These effects justify the oral LTA activity previously observed.

Highlights

One of the major groups of bacteria with demonstrated probiotic activity is the lactic acid bacteria group, the Lactobacillus species
The concentration of 50 μg/mL of lipoteichoic acid (LTA) increased the expression of surface MHC-II (IAb) and CD86 in bone marrow-derived dendritic cells (BMDC) to a similar extent of that observed in BMDC stimulated with 0.2 μg/mL E. coli LPS (Figure 1A)
Even though LTA isolated from other bacterial sources induced IL-12 secretion by BMDC [9,16,17], LTA from Lacticaseibacillus rhamnosus GG (LGG) was unable to upregulate neither IL-12p70 nor IL-12p40 secretion in our working conditions

Summary

Introduction

One of the major groups of bacteria with demonstrated probiotic activity is the lactic acid bacteria group, the (formerly) Lactobacillus species. The cell wall of Lacticaseibacillus, as with all Gram-positive bacteria, is composed mainly of lipoproteins, peptidoglycan, and lipoteichoic acid (LTA) The latter is considered analogous to lipopolysaccharide (LPS) in Gram-negative bacteria due to its similar biochemical and physiological properties. Lacticaseibacillus LTA is an amphiphilic molecule composed of a chain of poly-glycerophosphate with D-Ala substitutions and a hydrophobic anchor that allows its incorporation in the cell membrane [5]. It is an important ligand for the innate immune response [6]. The intraperitoneal administration of LpLTA impaired LPS-induced endotoxic shock in a mouse model [8]

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