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Activation of Natural Killer Cells in Patients with Chronic Bone and Joint Infection due to Staphylococci Expressing or Not the Small Colony Variant Phenotype.

Viel S, Rouzaire P, Laurent F, Walzer T, Bienvenu J, Valour F, Chidiac C, Ferry T, Group TL - Int J Chronic Dis (2014)

Bottom Line: We found that NK cells were activated in terms of CD69 expression, loss of CD16 and perforin, in all infected patients in comparison with healthy volunteers, independently of the SCV phenotype.Peripheral NK cells in patients with chronic BJI display signs of recent activation and degranulation in vivo in response to CD16-mediated signals, regardless of the type of bacteria involved.This could involve a universal capacity of isolates responsible for chronic BJI to produce undetectable SCVs in vivo, which might be a target of future intervention.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire d'Immunologie, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, 69310 Pierre-Bénite, France ; Université Claude Bernard Lyon 1, 69100 Villeurbanne, France ; Centre International de Recherche en Infectiologie, CIRI, Inserm U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 69007 Lyon, France.

ABSTRACT
Chronic bone and joint infections (BJI) are devastating diseases. Relapses are frequently observed, as some pathogens, especially staphylococci, can persist intracellularly by expressing a particular phenotype called small colony variant (SCV). As natural killer (NK) cells are lymphocytes specialized in the killing of host cells infected by intracellular pathogens, we studied NK cells of patients with chronic BJI due to staphylococci expressing or not SCVs (10 patients in both groups). Controls were patients infected with other bacteria without detectable expression of SCVs, and healthy volunteers. NK cell phenotype was evaluated from PBMCs by flow cytometry. Degranulation capacity was evaluated after stimulation with K562 cells in vitro. We found that NK cells were activated in terms of CD69 expression, loss of CD16 and perforin, in all infected patients in comparison with healthy volunteers, independently of the SCV phenotype. Peripheral NK cells in patients with chronic BJI display signs of recent activation and degranulation in vivo in response to CD16-mediated signals, regardless of the type of bacteria involved. This could involve a universal capacity of isolates responsible for chronic BJI to produce undetectable SCVs in vivo, which might be a target of future intervention.

No MeSH data available.


Related in: MedlinePlus

Absolute number of circulating NK cells (a) and their expression of CD69, CD16, and perforin ((b), (c), and (d), resp.) in each group of patients (*P < 0.05; **P < 0.001).
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fig1: Absolute number of circulating NK cells (a) and their expression of CD69, CD16, and perforin ((b), (c), and (d), resp.) in each group of patients (*P < 0.05; **P < 0.001).

Mentions: After obtaining the patient's consent, peripheral blood sampling was done at a median of 3 months after the diagnosis of chronic BJI. No significant difference between the SCV+ and SCV− groups was observed for the clinical parameters, except for the rate of recurrence, which was significantly higher in the SCV+ group (7/10 versus 0/10, P = 0.003) (Table 1). S. aureus, in comparison with coagulase-negative staphylococci, was involved in 7/10 and in 5/10 in patients belonging to the SCV+ and SCV− groups, respectively. Patients with other BJI were infected with Enterobacteriaceae (4 patients), P. acnes (1 patient), or P. aeruginosa (1 patient). Mean number of circulating lymphocytes was similar in all groups (1.99 G/L in HV group; 1.86 G/L in SCV+ BJI group; 1.91 G/L in SCV− BJI group; and 2.35 G/L in other BJI group). We investigated the function and phenotype of circulating CD56dim⁡ NK cells, the predominant subset in PBMCs. Their absolute number was similar in all groups (0.22 G/L in HV group; 0.26 G/L in SCV+ BJI group; 0.18 G/L in SCV− BJI group; and 0.29 G/L in other BJI group; Figure 1(a)). We observed an increased expression of CD69 from all staphylococci-infected patients, regardless of the SCV phenotype, indicative of an in vivo activation of NK cells (3.2% and 3.8% in SCV+ and SCV− BJI groups, resp.; in comparison with HV group, 2.3%; Figure 1(b)). Similarly, NK cells from all bacteria-infected patients displayed reduced perforin (MFI perforin+ NK cells of 28′589 in SCV+ BJI group; 23′762 in SCV− BJI group; and 23′027 in other BJI group, in comparison with 36′122 in HV group) and CD16 (MFI CD16 CD56dim⁡ NK cells of 27′473 in SCV+ BJI group; 28′711 in SCV− BJI group; and 27′568 in other BJI group, in comparison with 40′414 in HV group) expression that could be due to CD16-dependent in vivo cytotoxicity (Figures 1(c) and 1(d), resp.). The level of different other NK cell receptors (NKG2D, NKp30, DNAM1, and 2B4) was similar in all groups. Moreover, in response to stimulation with K562 cells, degranulation (12.9%, 16.7%, and 14.2% of CD107a+ NK cells in SCV+, SCV−, and other BJI groups, resp.) and IFN-γ production (6.9%, 8.9%, and 9.7% of IFNγ+ NK cells in SCV+, SCV−, and other BJI groups, resp.) by NK cells were found to be similar in all patient groups (Figure 2).


Activation of Natural Killer Cells in Patients with Chronic Bone and Joint Infection due to Staphylococci Expressing or Not the Small Colony Variant Phenotype.

Viel S, Rouzaire P, Laurent F, Walzer T, Bienvenu J, Valour F, Chidiac C, Ferry T, Group TL - Int J Chronic Dis (2014)

Absolute number of circulating NK cells (a) and their expression of CD69, CD16, and perforin ((b), (c), and (d), resp.) in each group of patients (*P < 0.05; **P < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4590914&req=5

fig1: Absolute number of circulating NK cells (a) and their expression of CD69, CD16, and perforin ((b), (c), and (d), resp.) in each group of patients (*P < 0.05; **P < 0.001).
Mentions: After obtaining the patient's consent, peripheral blood sampling was done at a median of 3 months after the diagnosis of chronic BJI. No significant difference between the SCV+ and SCV− groups was observed for the clinical parameters, except for the rate of recurrence, which was significantly higher in the SCV+ group (7/10 versus 0/10, P = 0.003) (Table 1). S. aureus, in comparison with coagulase-negative staphylococci, was involved in 7/10 and in 5/10 in patients belonging to the SCV+ and SCV− groups, respectively. Patients with other BJI were infected with Enterobacteriaceae (4 patients), P. acnes (1 patient), or P. aeruginosa (1 patient). Mean number of circulating lymphocytes was similar in all groups (1.99 G/L in HV group; 1.86 G/L in SCV+ BJI group; 1.91 G/L in SCV− BJI group; and 2.35 G/L in other BJI group). We investigated the function and phenotype of circulating CD56dim⁡ NK cells, the predominant subset in PBMCs. Their absolute number was similar in all groups (0.22 G/L in HV group; 0.26 G/L in SCV+ BJI group; 0.18 G/L in SCV− BJI group; and 0.29 G/L in other BJI group; Figure 1(a)). We observed an increased expression of CD69 from all staphylococci-infected patients, regardless of the SCV phenotype, indicative of an in vivo activation of NK cells (3.2% and 3.8% in SCV+ and SCV− BJI groups, resp.; in comparison with HV group, 2.3%; Figure 1(b)). Similarly, NK cells from all bacteria-infected patients displayed reduced perforin (MFI perforin+ NK cells of 28′589 in SCV+ BJI group; 23′762 in SCV− BJI group; and 23′027 in other BJI group, in comparison with 36′122 in HV group) and CD16 (MFI CD16 CD56dim⁡ NK cells of 27′473 in SCV+ BJI group; 28′711 in SCV− BJI group; and 27′568 in other BJI group, in comparison with 40′414 in HV group) expression that could be due to CD16-dependent in vivo cytotoxicity (Figures 1(c) and 1(d), resp.). The level of different other NK cell receptors (NKG2D, NKp30, DNAM1, and 2B4) was similar in all groups. Moreover, in response to stimulation with K562 cells, degranulation (12.9%, 16.7%, and 14.2% of CD107a+ NK cells in SCV+, SCV−, and other BJI groups, resp.) and IFN-γ production (6.9%, 8.9%, and 9.7% of IFNγ+ NK cells in SCV+, SCV−, and other BJI groups, resp.) by NK cells were found to be similar in all patient groups (Figure 2).

Bottom Line: We found that NK cells were activated in terms of CD69 expression, loss of CD16 and perforin, in all infected patients in comparison with healthy volunteers, independently of the SCV phenotype.Peripheral NK cells in patients with chronic BJI display signs of recent activation and degranulation in vivo in response to CD16-mediated signals, regardless of the type of bacteria involved.This could involve a universal capacity of isolates responsible for chronic BJI to produce undetectable SCVs in vivo, which might be a target of future intervention.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire d'Immunologie, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, 69310 Pierre-Bénite, France ; Université Claude Bernard Lyon 1, 69100 Villeurbanne, France ; Centre International de Recherche en Infectiologie, CIRI, Inserm U1111, CNRS UMR5308, ENS de Lyon, UCBL1, 69007 Lyon, France.

ABSTRACT
Chronic bone and joint infections (BJI) are devastating diseases. Relapses are frequently observed, as some pathogens, especially staphylococci, can persist intracellularly by expressing a particular phenotype called small colony variant (SCV). As natural killer (NK) cells are lymphocytes specialized in the killing of host cells infected by intracellular pathogens, we studied NK cells of patients with chronic BJI due to staphylococci expressing or not SCVs (10 patients in both groups). Controls were patients infected with other bacteria without detectable expression of SCVs, and healthy volunteers. NK cell phenotype was evaluated from PBMCs by flow cytometry. Degranulation capacity was evaluated after stimulation with K562 cells in vitro. We found that NK cells were activated in terms of CD69 expression, loss of CD16 and perforin, in all infected patients in comparison with healthy volunteers, independently of the SCV phenotype. Peripheral NK cells in patients with chronic BJI display signs of recent activation and degranulation in vivo in response to CD16-mediated signals, regardless of the type of bacteria involved. This could involve a universal capacity of isolates responsible for chronic BJI to produce undetectable SCVs in vivo, which might be a target of future intervention.

No MeSH data available.


Related in: MedlinePlus