AUTHOR=Song Jie , Lang Fengchao , Zhao Na , Guo Yan , Zhang Huatang 

TITLE=Vaginal Lactobacilli Induce Differentiation of Monocytic Precursors Toward Langerhans-like Cells: in Vitro Evidence

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02437

DOI=10.3389/fimmu.2018.02437

ISSN=1664-3224

ABSTRACT=<p>Lactobacilli have immunomodulatory mechanisms that affect the host cell immune system, leading to inhibition of HIV-1 transmission. Thus, lactobacilli as mucosal delivery vehicles for developing HIV-1 vaccines have attracted interest in recent years. Herein, we investigated the immunomodulatory effects of six strains of <italic>Lactobacillus</italic> naturally isolated from vaginal samples, including <italic>Lactobacillus crispatus</italic> (<italic>L. crispatus), L. fermentum, L. jensenii, L. gasseri, L. delbrueckii</italic> and <italic>L. johnsonii</italic>, on differentiation of monocytic precursors. <italic>L. crispatus, L. fermentum</italic> and <italic>L. delbrueckii</italic> could drive human monocytic cell line THP-1 cells to differentiate into dendritic-like cells according to the morphology. Moreover, <italic>L. crispatus</italic> increased costimulatory molecules including CD40, CD80 and CD86, and Langerhans cell specific C-type lectin receptors CD207, while <italic>L. fermentum</italic> decreased these molecules in THP-1 cells. Furthermore, <italic>L. crispatus</italic> promoted the differentiation of THP-1 cells with specific markers, phagocytic features, cytokine production ability and reduced the expression of receptors for HIV-1 entry of Langerhans cells. However, in the presence of <italic>L. fermentum</italic>, THP-1 cells did not show the above alterations. Moreover, similar effects of <italic>L. crispatus</italic> and <italic>L. fermentum</italic> were observed in CD14<sup>+</sup> monocytes. These data suggested that <italic>L. crispatus</italic> facilitates the differentiation of monocytic precursors toward Langerhans-like cells <italic>in vitro</italic>. We further identified the cell wall components of <italic>Lactobacillus</italic> and found that peptidoglycans (PGNs), rather than bacteriocins, S-layer protein and lipoteichoic acid, were key contributors to the induction of CD207 expression. However, PGNs originating from <italic>Bacillus subtilis, E. coli</italic> JM109 and <italic>E. coli</italic> DH5α did not elevate CD207 expression, indicating that only PGN derived from <italic>Lactobacillus</italic> could enhance CD207 expression. Finally, the recognized receptors of <italic>L. crispatus</italic> (such as TLR2 and TLR6) and the upstream transcription factors (PU.1, TAL1, TIF1γ, and POLR2A) of CD207 were examined, and the expression of these molecules was enhanced in THP-1 cells following <italic>L. crispatus</italic> treatment. Thus, this study offers powerful evidence that vaginal lactobacilli modulate monocytic precursor differentiation into Langerhans-like cells probably via activating the TLR2/6-TFs-CD207 axis. These data provide clues for further investigation of the original occurrence, development and differentiation of Langerhans cells from monocytes.</p>