Release of LL-37 by Activated Human Vγ9Vδ2 T Cells: A Microbicidal Weapon against Brucella suis

Abstract

Human Vγ9Vδ2 T cells play a crucial role in early immune response to intracellular pathogens. Moreover, in brucellosis, these cells are drastically increased in the peripheral blood of patients during the acute phase of infection. In vitro, Vγ9Vδ2 T cells are capable of inhibiting Brucella growth and development through a combination of mechanisms: 1) cytotoxicity, 2) macrophage activation and bactericidal activity through cytokine and chemokine secretion, and 3) antibacterial effects. We previously described that antibacterial factors were found in supernatants from activated Vγ9Vδ2 T cells. In this study, we show that Vγ9Vδ2 T cells express the human cathelicidin hCAP18 and its mature form, known as LL-37, is released upon activation of Vγ9Vδ2 T cells. We also show that LL-37 has an antibacterial effect on Brucella suis. Overall, our results demonstrate that LL-37 is a soluble factor responsible for a part of the bactericidal activity of Vγ9Vδ2 T cells.

Increased Frequencies of Circulating IFN-γ-Producing Vδ1+and Vδ2+γδ T Cells in Patients with Asymptomatic Persistent Hepatitis B Virus Infection

“…Vd2 T cells are the predominant cd T cell subset in human blood and are capable of producing IFN-c and TNF-a (23,24), killing target cells (3,22,23), inducing activation and maturation of neutrophils (15,16), monocytes (24), Bcells (7,9), and dendritic cells (14,23,35), and presenting antigen to conventional CD4 + and CD8 + T cells (8). Their multifunctional capacity makes them ideal candidates for immunotherapy, and they are already the focus of several clinical trials (5,12,20,42,51).…”

Staphylococcus epidermidis Isolated From Newborn Infants Express Pilus-Like Structures and Are Inhibited by the Cathelicidin-Derived Antimicrobial Peptide LL37

“…Antimicrobial susceptibility of S. epidermidis (CI-1-13; ATCC 12228; ATCC 35984; ATCC 29213; ATCC 25922) was performed with the microdilution broth method according to the recommendations of the Clinical and Laboratory Standards Institute (CLSI; 21). Refined Mueller Hinton broth (MHB; BD Diagnostic systems, NJ) was used as described earlier, because standard MHB has been found to underestimate the activity of antimicrobial peptides (22,23). Becasue S. epidermidis were unable to grow in refined MHB, a 1:1 mixture of regular MHB and refined MHB was used for the experiments.…”

Type I Interferon Induction during Influenza Virus Infection Increases Susceptibility to Secondary Streptococcus pneumoniae Infection by Negative Regulation of γδ T Cells

“…In secondary and tertiary lymphoid organs, ␥␦ T cells are able to respond directly to pathogen-associated molecular patterns (PAMPs) and cytokines in the absence of cognate TCR ligands. They kill the infected cells through pathways such as Fas or TRAIL and contribute to pathogen clearance by the release of cytotoxic and/or antimicrobial molecules (12,13,35). ␥␦ T cells are rapidly activated, producing IFN-␥, tumor necrosis factor alpha (TNF-␣), and IL-17 in several mouse models of bacterial infection with Mycobacterium bovis, Listeria monocytogenes, and Salmonella enterica (15,38,47).…”