NK cells from tuberculous pleurisy express high ICAM‐1 levels and exert stimulatory effect on local T cells

Abstract

Tuberculous pleurisy, one of the most common manifestations of extrapulmonary tuberculosis, is characterized by a T-cell-mediated hypersensitivity reaction along with a Th1 immune profile. In this study, we investigated functional cross-talk among T and NK cells in human tuberculous pleurisy. We found that endogenously activated pleural fluidderived NK cells express high ICAM-1 levels and induce T-cell activation ex vivo through ICAM-1. Besides, upon in vitro stimulation with monokines and PAMP, resting peripheral blood NK cells increased ICAM-1 expression leading to cellular activation and Th1 polarization of autologous T cells. Furthermore, these effects were abolished by anti-ICAM-1 Ab. Hence, NK cells may contribute to the adaptive immune response by a direct cellcontact-dependent mechanism in the context of Mycobacterium tuberculosis infection.Key words: ICAM-1 . NK cells . Pleurisy . Th1 . Tuberculosis Supporting Information available online IntroductionPleuritis is the most frequent clinical manifestation of extrapulmonary tuberculosis (TB) among young adults, and is normally considered a relatively benign form of disease since it may resolve without chemotherapy [1]. Tuberculous pleurisy is caused by a severe delayed-type hypersensitivity reaction in response to the rupture of a subpleural focus of Mycobacterium tuberculosis (Mtb) infection, but it may also be developed as a complication of primary pulmonary TB [2,3]. This pleural effusion is characterized by a strong granulomatous inflammatory response to Mtb together with high levels of . NK cells are CD56 1 CD16 1/À /CD3 À CD19 À lymphocytes of the innate immune system whose function is controlled by an array of germline-encoded activator/inhibitory receptors [5,6]. Two subsets of NK cells have been identified in humans according to CD56 expression differing in phenotype and function, and also in terms of chemokine receptors and adhesion molecules expression [7,8,9]. Functionally, CD56 bright cells are effective cytokine producers, whereas CD56 dim cells are efficient effectors of natural and Ab-dependent target cell lysis. Recently, we have described that an endogenously activated pleural fluid NK (PF-NK) population is a major source of IFN-g in response to Mtb [10,11]. Consistently, PF-NK are enriched in CD56 bright cells, as has been observed in other chronic inflammatory sites [12,13] or in tumor-affected tissues [14]. Together with the classical NK functions (i.e. cytotoxicity and cytokine production), novel skills have recently been described in niche-specific and in vitro-activated human NK cells. These unconventional capabilities include [16,17,18] and direct pathogen recognition [19,20]. In this regard, a novel innate immune cell population called Interferon-producing killer dendritic cells has been recently described in mice [21,22].ICAM-1/CD54 is the major ligand of costimulatory a L b 2 integrin (CD11a/CD18), commonly known as lymphocyte function-associated antigen (LFA-1) [23,24]. The surface enhancement of ICAM-1 on endothelial, APC and...

Role Played by the Programmed Death‐1–Programmed Death Ligand Pathway during Innate Immunity againstMycobacterium tuberculosis

“…Natural killer (NK) cells present in tuberculous fluids (PFNK cells) express a differential pattern of molecules that participates in their migration to the lung and in the modulation of the immune response and T cell activation [3], addressing the importance of innate immunity to fight this pathogen.…”

“…to the lung and in the modulation of the immune response and T cell activation [3], addressing the importance of innate immunity to fight this pathogen.…”

Mycobacterium tuberculosis Multidrug Resistant Strain M Induces an Altered Activation of Cytotoxic CD8+ T Cells

“…Expression of lytic molecules can be down-regulated by differentiation and maturation [24], [28] or up-regulated by activation [29] of CD8 + T cells. Therefore, expansion of memory CD8 + T cells as well as early activation marker CD69 and late activation marker CD25 were measured in CD8 + T cells at different time points upon Mtb stimulation.…”

“…The ability of Mtb -stimulated CD8 + T cells to bind to Mtb -pulsed Mφ was determined by flow cytometry (FACS) as previously described [24]. 5-d cultured Mφ were detached from culture plates by gentle pipetting with ice-cold RPMI medium, washed, suspended in PBS-0.1% BSA at 2.5×10 6 cells/ml and incubated with 2 µM CFSE (Invitrogen, USA) for 30 min at 37°C.…”

Role of NK Cells in Tuberculous Pleurisy as Innate Promoters of Local Type 1 Immunity with Potential Application on Differential Diagnosis

“…Besides, Mtb stimulated IFN-production by NK shows Ag-specific features, given that pleural NK cells derived from non TB patients' lack of this response. According to these findings, we realized that pleural NK cells properties could be utilized in an innate immune cell based assay for differential diagnosis of tuberculous pleurisy (Schierloh et al, 2008Schierloh et al, 2005aSchierloh et al, , 2007Schierloh et al, , 2009. The finding that immunoregulatory CD56 bright NK subset showing cellular activation features are strongly enriched among pleural NK cells was interesting given that these cells are known to link innate with adaptative immunity in a number of intracellular infections (Artavanis-Tsakonas et al, 2003;Culley, 2009;Fehniger et al, 2003).…”