Intestinal lamina propria macrophages upregulate interleukin-10 mRNA in response to signals from commensal bacteria recognized by MGL1/CD301a

Abstract

Ligand-induced cellular signaling involved in interleukin 10 (IL-10) production by lamina propria macrophages (LPMs) during their interactions with commensal bacteria is not clearly understood. We previously showed, using mice lacking a C-type lectin MGL1/CD301a, that this molecule on colonic LPMs plays an important role in the induction of IL-10 upon interaction with commensal bacteria, Streptococcus sp. In the present report we show that the physical engagement of MGL1/CD301a on LPMs with in-situ isolated Streptococcus sp. bacteria leads to IL-10 mRNA induction. Spleen tyrosine kinase (Syk), caspase recruitment domain 9 (CARD9), and extracellular signal-regulated kinase (ERK), but not NF-κB pathway, are shown to be indispensable for IL-10 mRNA induction after stimulation with heat-killed Streptococcus sp. Guanidine hydrochloride treatment of Streptococcus sp., which is known to extract bacterial cell surface glycan-rich components, abolished bacterial binding to recombinant MGL1/CD301a. The extract contained materials which bound rMGL1 in ELISA and appeared to induce IL-10 mRNA expression in LPMs in vitro. Lectin blotting showed that the extract contained glycoproteins which are considered as putative ligands for MGL1. Some human commensal Lactobacillus species also induced IL-10 mRNA expression by colonic LPMs in vitro, which depends on the presence of MGL1/CD301a and CARD9. The present results are the first to show that MGL1/CD301a acts as a signal transducer during colonic host–microbe interactions.

GiardiaIncreases Macrophage Production of the Anti-Inflammatory Cytokine Interleukin-10 in Response to Lipopolysaccharide via Macrophage Galactose Binding Lectin (MGL1)

“…Lamina propria macrophages, in fact, interact directly with glycoproteins on the surface of the commensal Streptococcus sp . to release IL-10 (Kurashina et al 2021).…”

“…An increase of anti-inflammatory cytokines in response to MGL1 and TLR4 co-stimulation could help explain the findings of reduced diarrheal burden yet the presence of Giardia in control stools (Kotloff et al 2013). Notably, MGL1 has been previously shown to upregulate the IL-10 response in peritoneal macrophages (Kurashina et al 2021). Additionally, MGL1 and TLR2 activation have been shown to synergize in the production of IL-10 and TNF-□ (van Vliet et al 2013).…”

High-throughput probing macrophage–bacteria interactions at the single cell level with microdroplets

“…[41][42][43][44] As countermeasures, intestinal commensal bacteria could stimulate lamina propria macrophages to secrete interleukin-10 (IL-10) leading to the suppressed inflammatory state of macrophages. 13,45 Therefore, the interactive relationships between macrophages and bacteria deserve more efforts of systematic investigation. Microfluidic devices have been proposed to study the cell-tocell interactions as a useful tool.…”

Association of intestinal dysbiosis with susceptibility to multiple sclerosis: Evidence from different population studies (Review)

“…In a mouse study, direct binding of Streptococcus sp. and Lactobacillus ligands initiates a signaling cascade that induces increased expression of IL-10 by C-type lectin-positive macrophages and macrophage galactose-type lectin-1/CD301a, and downstream mediators such as spleen tyrosine kinase, caspase recruitment domain-containing protein 9 and ERK are also involved in the induction of IL-10 mRNA (69). The immunoregulatory effects of this cytokine are critical for brain health, as indicated by another study of oxygen and glucose deprivation-induced cerebral ischemia, as IL-10 has an immunoregulatory role that attenuates neuronal death and promotes neurite growth and synapse formation through the JAK1/STAT3 pathway (70).…”