Toll-like receptor 2-mediated induction of human beta-defensin 2 expression by Leptospira interrogans in human kidney cells

Naharuthai Inthasin,¹ Chawikan Boonwong,² Sutthicha Matamnan,² Jintapa Sueasuay,¹ Patimaporn Wongprompitak,¹ Wiwit Tanttibhedhyangkul,¹ Pattama Ekpo^1,2

Affiliations:
¹ Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
² Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

Abstract

Background: Leptospirosis is a zoonotic disease caused by Leptospira interrogans. Severe leptospirosis is often accompanied by kidney dysfunction caused by chronic infection. The kidney pathology involves bacterial invasion and inflammation caused by pro-inflammatory cytokines. Human beta defensins (hBDs) are antimicrobial peptides induced by microbial infection and/or pro-inflammatory cytokines. One function of hBDs is the recruitment of immune cells that leads to inflammation. However, the expression of hBDs by kidney epithelium in response to pathogenic Leptospira has never been investigated.
Objective: To determine the expression of hBDs in human kidney epithelium responses to Leptospira.
Methods: Human kidney cells were infected with Leptospira interrogans serovar Autumnalis in the presence or absence of anti-TLR2 neutralizing antibody (Ab) for 6 hours. TLR2, hBDs and pro-inflammatory cytokines mRNA expressions were analyzed by quantitative polymerase chain reaction (qPCR).
Results: Pathogenic Leptospira upregulated the expressions of pro-inflammatory cytokines and hBD2, but not TLR2, hBD1 and hBD3 in kidney cells. The expressions of hBD2 and pro-inflammatory cytokines were inhibited in the presence of anti-hTLR2 neutralizing Ab.
Conclusions: Our results provide the first evidence that pathogenic Leptospira induces hBD2 expression in kidney cells. The expressions of pro-inflammatory cytokines and hBD2 in the cells in response to pathogenic Leptospira are regulated by TLR2. Pro-inflammatory cytokines and hBD2 might be play role in recruitment of immune cells to the kidney and contribute to the development of inflammation-mediated tissue damage in the kidney. However, further study is needed to improve the understanding of the role of these molecules in immune response activation.
Key words: TLR2, leptospirosis, kidney epithelium, human beta-defensins, Leptospira