Probiotic bacterial strains differentially modulate macrophage cytokine production in a strain-dependent and cell subset-specific manner

Abstract

Gut mucosal macrophages play a pivotal role in driving mucosal immune responses, resulting in either activation of inflammatory immune responses to pathogenic challenge or tolerance to beneficial luminal contents such as food and commensal bacteria. Macrophage responses elicited are dependent on tissue environment and the resulting cell subset, where homeostatic macrophages resemble the M2 macrophage subset and inflammatory macrophages resemble M1s. Probiotics can modulate macrophage function with outcome dependent on subset present. Using a THP-1 monocyte cell line-derived model of CD14high/low M1 and M2 macrophages, the aim of this study was to investigate the immunomodulatory effects of a panel of heat-killed probiotic bacteria and their secreted proteins on the subset-specific inflammatory marker profile of TNFα, IL-6 and NFκB. M1 and M2 cells were generated by differentiation of monocyte stable transfectants for high and low CD14 expression with phorbol 12-myristate 13-acetate and vitamin D3, respectively, where the resulting CD14lo M2 and CD14hi M1s mimicked homeostatic and inflammatory mucosal macrophages. Subsets were stimulated by enteropathic lipopolysaccharides in the presence or absence of heat-killed (HK) or secreted proteins (SP) from a panel of probiotic bacteria. Regulation of cytokine expression was measured by ELISA and NFκB activity by reporter assay. HK probiotics suppress CD14lo and augment CD14hi M1 and M2 production of TNFα whereas SPs augmented CD14hi M1 TNFα and were generally suppressive in the other subtypes. M2 macrophage IL-6 production was suppressed by both HK and SPs and differentially regulated in CD14lo and CD14hi M1s. NFκB activation failed to parallel the regulatory profiles for TNFα and IL-6 which is suggestive of probiotic bacteria exerting their regulatory effects on these cytokines in an NFκB-independent manner. In conclusion, HK and SP probiotics differentially regulate macrophage cytokines and NFκB activation in a subset-dependent manner and suggest a cautionary approach to probiotic treatment of mucosal inflammation.

Lactobacillus acidophilus attenuates Aeromonas hydrophila induced cytotoxicity in catla thymus macrophages by modulating oxidative stress and inflammation

“…In contrary, Salinas et al (2008a) have earlier reported that L. delbrueckii induced apoptosis in teleost fish cell lines. Thus, the inhibitory effect of probiotics against pathogens may be strain specific (Habil et al, 2011). Therefore, each probiotic candidate needs to be screened in-vitro and in-vivo before being employed as dietary supplements in aquaculture practice.…”

S-Layer Protein Mediates the Stimulatory Effect of Lactobacillus helveticus MIMLh5 on Innate Immunity

“…This finding suggests that MIMLh5 bacterial cells could be more prone to induce an anti-inflammatory response in this cellular system than U937 cells and BMDMs. Such different behavior can be explained by considering that different immune responses can be induced by the same stimulus depending on the cell type, origin, and polarization (70). Moreover, because BMDMs and U937 cells have been maturated in vitro, it is plausible that they are less physiological than PCMs and that they could not possess all the features of matured macrophages.…”

ProbioticLactobacillusStrains Stimulate the Inflammatory Response and Activate Human Macrophages

“…In addition, Li et al [11] showed that live and heat-killed LGG are able to exert similar effects on the secretion of pro- and anti-inflammatory cytokines and chemokines when included in the diet of infant rats. However, these beneficial effects have been associated with only a limited number of strains, and other strains and species cannot be presumed to exert the same effects [12, 13]. The immune effects of probiotic bacteria have therefore been shown to be extremely diverse and strain-dependent in addition to cell type-specific.…”