Lactobacilli Regulate Staphylococcus aureus 161:2-Induced Pro-Inflammatory T-Cell Responses In Vitro

Abstract

There seems to be a correlation between early gut microbiota composition and postnatal immune development. Alteration in the microbial composition early in life has been associated with immune mediated diseases, such as autoimmunity and allergy. We have previously observed associations between the presence of lactobacilli and Staphylococcus (S.) aureus in the early-life gut microbiota, cytokine responses and allergy development in children. Consistent with the objective to understand how bacteria modulate the cytokine response of intestinal epithelial cell (IEC) lines and immune cells, we exposed IEC lines (HT29, SW480) to UV-killed bacteria and/or culture supernatants (-sn) from seven Lactobacillus strains and three S. aureus strains, while peripheral blood mononuclear cells (PBMC) and cord blood mononuclear cells (CBMC) from healthy donors were stimulated by bacteria-sn or with bacteria conditioned IEC-sn. Although the overall IEC response to bacterial exposure was characterized by limited sets of cytokine and chemokine production, S. aureus 161:2-sn induced an inflammatory response in the IEC, characterized by CXCL1/GROα and CXCL8/IL-8 production, partly in a MyD88-dependent manner. UV-killed bacteria did not induce a response in the IEC line, and a combination of both UV-killed bacteria and the bacteria-sn had no additive effect to that of the supernatant alone. In PBMC, most of the Lactobacillus-sn and S. aureus-sn strains were able to induce a wide array of cytokines, but only S. aureus-sn induced the T-cell associated cytokines IL-2, IL-17 and IFN-γ, independently of IEC-produced factors, and induced up regulation of CTLA-4 expression and IL-10 production by T-regulatory cells. Notably, S. aureus-sn-induced T-cell production of IFN- γ and IL-17 was down regulated by the simultaneous presence of any of the different Lactobacillus strains, while the IEC CXCL8/IL-8 response was unaltered. Thus these studies present a possible role for lactobacilli in induction of immune cell regulation, although the mechanisms need to be further elucidated.

Lactobacillus reuteri and Staphylococcus aureus differentially influence the generation of monocyte‐derived dendritic cells and subsequent autologous T cell responses

“…While an early-life gut microbiota positive for lactobacilli was associated with a regulated immunological profile and protection against allergy development in children, early colonization with S. aureus was associated with strong in vitro immune responses, particularly when lactobacilli were not detected. These associations between in vivo colonization and immune responsiveness in vitro have been confirmed in further studies-and we have observed that while different lactobacilli (e.g., Lactobacillus [L.] reuteri and L. rhamnosus) readily activate innate immune cells like monocytes, they are capable of dampening S. aureusinduced immune activation of adaptive immune cells like T cells in vitro [22]. Recently, we have also shown that L. reuteri has a significant impact on (the maturation of) both conventional and retinoic acid-derived DC in making them less responsive to an inflammatory challenge [23].…”

“…In our model, it is likely that SE have bound MHC on the DC that are capable of activating T cells, even though the CFS was added just once at day 3 of DC generation and that substantial washing of the DC was performed before co‐culture. However, we have previously shown that this S. aureus ‐CFS induces inflammatory responses by intestinal epithelial cells, which might indicate its potential to use other mechanisms to activate cells than via the obvious MHC–TCR interaction .…”

“…Recently, it has been shown that breast‐feeding plays a vital role in the early colonization with S. aureus and different lactobacilli, and that the nutrients in breast milk helps in maintaining these microbes in the infant gut . We have previously shown that lactobacilli dampen S. aureus ‐CFS‐induced PBMC responses . Further, we have recently observed that the dampening effect might be mediated in different ways depending on the responding immune cell ( Johansson, Björkander et al unpublished observation ).…”

“…These associations between in vivo colonization and immune responsiveness in vitro have been confirmed in further studies—and we have observed that while different lactobacilli (e.g., Lactobacillus [ L .] reuteri and L. rhamnosus ) readily activate innate immune cells like monocytes, they are capable of dampening S. aureus ‐induced immune activation of adaptive immune cells like T cells in vitro . Recently, we have also shown that L. reuteri has a significant impact on (the maturation of) both conventional and retinoic acid‐derived DC in making them less responsive to an inflammatory challenge .…”

The Role of <i>L. plantarum</i> as an Immunomodulator Secretion of <i>Transforming Growth Factor</i>-β1, <i>Transforming Growth Factor</i>-β3, and <i>Interferon</i>-α Macrophages and Dermal Fibroblasts

“…Many researchers have understood that the surface microflora affects the innate and adaptive immune system. The beneficial effect of microflora in the gastrointestinal tract supports the use of probiotic [17]. Probiotic in the process of wound healing has been used by the researchers with the promising result [18], [19].…”