The B subunit of Escherichia coli heat‐labile toxin alters the development and antigen‐presenting capacity of dendritic cells

Abstract

Escherichia coli’s heat-labile enterotoxin (Etx) and its non-toxic B subunit (EtxB) have been characterized as adjuvants capable of enhancing T cell responses to co-administered antigen. Here, we investigate the direct effect of intravenously administered EtxB on the size of the dendritic and myeloid cell populations in spleen. EtxB treatment appears to enhance the development and turnover of dendritic and myeloid cells from precursors within the spleen. EtxB treatment also gives a dendritic cell (DC) population with higher viability and lower activation status based on the reduced expression of MHC-II, CD80 and CD86. In this respect, the in vivo effect of EtxB differs from that of the highly inflammatory mediator lipopolysaccharide. In in vitro bone marrow cultures, EtxB treatment was also found to enhance the development of DC from precursors dependent on Flt3L. In terms of the in vivo effect of EtxB on CD4 and CD8 T cell responses in mice, the interaction of EtxB directly with DC was demonstrated following conditional depletion of CD11c+ DC. In summary, all results are consistent with EtxB displaying adjuvant ability by enhancing the turnover of DC in spleen, leading to newly mature myeloid and DC in spleen, thereby increasing DC capacity to perform as antigen-presenting cells on encounter with T cells.

Adjuvant-Mediated Epitope Specificity and Enhanced Neutralizing Activity of Antibodies Targeting Dengue Virus Envelope Protein

“…Here, and in previous reports, we have demonstrated that LT derivatives shape the epitope recognition profile of antibodies to different pathogens [( 12 ), unpublished data]. Previous studies have demonstrated that LT derivatives improve the expression of co-stimulatory molecules on B lymphocytes and dendritic cells and, consequently, on prime CD4 + T cells, leading to modulation of Th1/Th2/Th17 cytokine production patterns ( 12 , 17 , 19 , 71 – 73 ). Although future studies will have to be performed, the capacity to program B cells using cognate T helper lymphocytes, concomitant with direct activation effects, may represent possible alternatives to explain the action of LT derivatives on the modulation of the epitope recognition pattern of antibodies.…”

E. coli Enterotoxin LtB Enhances Vaccine-Induced Anti-H. pylori Protection by Promoting Leukocyte Migration into Gastric Mucus via Inflammatory Lesions

“…However, despite the observation of LtB potent adjuvanticity, the mechanism beneath LtB enhancement of the protective effect remains unclear [32]. LtB could bind to the GM1 ganglioside receptor, affect the turnover, development and antigen presentation of dendritic cells, clustering of lymphocytes, and B cell uptaking antigens [14,33]. Most reports show LtB/mutant Lt-assisted mucosal vaccination may produce enhanced Th1, Th1/Th2, Th1/Th17, or Th1/Th2/Th17 type immune responses, while Th1/Th17 bias reaction is thought to be associated with the anti-H. pylori immune protection [34,35,36].…”

Parenteral adjuvant potential of recombinant B subunit of Escherichia coli heat-labile enterotoxin

“…The immune-stimulatory effect of rLTB may be the result of five factors: (1) augmenting antigen presentation by both MHC classes I and II ( Nashar et al 2001 , Zhang et al. 2016 ); (2) activating selective lymphocyte differentiation ( Williams 2000 ); (3) causing dendritic cell activation and maturation ( Ji et al 2015 ); (4) inducing B7-2 expression on antigen-presenting cells following co-stimulation of CD4 + lymphocytes ( Yamamoto et al 2001 ); and (5) augmenting expression of B lymphocyte activation markers such as MHC class II, B7, CD40, CD25, and ICAM-1 ( Nashar et al 1997 ).…”