Our previous studies show that hepatic natural killer T (NKT) cells play a significant role in the pathogenesis of NAFLD. In this study, we explore the mechanism by which modification of gut flora leads to the alteration of hepatic NKT cells and improvement of steatosis. Mice were fed a high-fat (HF) diet to induce NAFLD. Some of them also received different doses of mixed-strain probiotics (VSL#3); single-strain probiotic (Bifidobacterium infantis) or antibiotics. Animal weight, glucose tolerance, liver steatosis and hepatic NKT cells were assessed. Lipid extracts from probiotics were tested for their ability to activate NKT

cells. Toll-like receptor 4 (TLR4) knockout mice p38 MAPK activity were also evaluated for their responses to HF diet. High-dose VSL#3 was more effective

than low-dose VSL#3 and B. infantis for the improvement of hepatic NKT cell depletion and steatosis. The lipids extracted from VSL#3 stimulated NKT cells both in vivo and in vitro. In contrast, lipids Seliciclib manufacturer from B. infantis decreased α-GalCer-mediated NKT cell activation in vitro, but were able to stimulate NKT cells. TLR4 knockout mice have a similar response to HF-diet-induced NKT cell depletion and obesity. These results suggest that alterations in the gut flora have profound effects on hepatic NKT cells and steatosis, which are both strain-specific and dose-dependent, but not through TLR4 signalling. Furthermore, these data suggest that probiotics may contain bacterial glycolipid antigens that directly modulate the effector functions of hepatic NKT cells. “
“Citation Wang B, Koga K, Osuga Y, Hirata T, Saito A, Yoshino O, Hirota Y, Harada M, Takemura Y, Fujii T, Taketani Y. High mobility group Box 1 (HMGB1) levels in the placenta and in serum in preeclampsia. Am J Reprod Immunol 2011; 66: 143–148 Problem Preeclampsia is a pregnancy disorder characterized

by systemic inflammation. High mobility group box 1 (HMGB1) Tangeritin is a molecule known to act as a ‘danger signal’ by participating in various inflammatory processes, but data in regard to preeclampsia are sparse. The aim of this study was to analyze placental and serum HMGB1 levels in normal pregnancy and preeclampsia. Method of study Sera were collected from women with preeclampsia soon after the manifestation of the disease and before commencing any medication. Placental samples were collected immediately after delivery. Expressed isoforms of HMGB1 (28- and 30-kDa) in the placenta were evaluated by Western blot analysis. Serum HMGB1 concentrations were measured using enzyme-linked immunosorbent assays (ELISA). Results Two isoforms of HMGB1 are expressed by the human placenta. The 28- and 30-kDa HMGB1 isoforms were expressed highly in preeclamptic placental tissue; however, compared with normotensive control tissue, differences in detected expression levels did not reach statistical significance.

Increased numbers of NKG2C+, NKG2A+, and CD161+ T cells were also associated to HCMV infection. The NKG2C deletion frequency ICG-001 mouse was comparable in children with congenital HCMV infection and controls. Remarkably, the homozygous

NKG2C+/+ genotype appeared associated with increased absolute numbers of NKG2C+ NK cells. Moreover, HCMV-infected NKG2C+/+ children displayed higher absolute numbers of NKG2A+ and total NK cells than NKG2C+/− individuals. Our study provides novel insights on the impact of HCMV infection on the homeostasis of the NK-cell compartment in children, revealing a modulatory influence of NKG2C copy number. Human cytomegalovirus (HCMV) infection is highly prevalent worldwide (50–100%), and usually follows a subclinical course in healthy individuals. The virus remains in a lifelong latent state, occasionally undergoing reactivation, but may have a pathogenic PD0325901 nmr role in immunodeficient and immunosuppressed patients [1-3]. Moreover, HCMV has been associated

with atherosclerosis, lymphoproliferative disorders, and glioblastoma, as well as with an accelerated immunosenescence and a shorter lifespan [4-7]. Vertical transmission of HCMV during pregnancy is considered the most common cause of congenital infection worldwide, affecting ∼0.2–2% of infants and potentially causing fetal lesions [8-10]. Though most infected newborns are asymptomatic, ∼10% display a variety of clinical disorders [8, 11] potentially leading to important

sequelae such as mental retardation and deafness. The type of maternal infection (i.e., primary versus reactivation/reinfection) conditions the risk of congenital infection and the pregnancy stage at which transmission occurs is related to clinical severity [12-16]. Maternal antibodies with neutralizing activity are transferred to the fetus predominantly during the third trimester of gestation and may prevent congenital CMV disease [17]. Chloroambucil Among other factors, fetal immune immaturity may determine the outcome of congenital infection [18, 19]. An effective defense against HCMV requires the participation of T and NK cells, and the virus has developed different immune evasion strategies [20]. Patients with congenital HCMV infection have been shown to display mature CD8+ T-cell responses [21, 22], and an expansion and differentiation of a specific TcR γδ+ cell subset has been recently reported [23]. In contrast, information on the role of NK cells in this context is rather limited [24, 25]. HCMV infection stably alters the distribution of NK-cell receptors (NKRs) in healthy adult blood donors and children.

3). Whether other previously designated IFN-inducible genes of pDCs such as MXA and CXCL10 also require NAB2 induction for their type I IFN-independent expression [13] remains to be determined. Staurosporine molecular weight While TLR-mediated signaling and IFN-R signaling can independently induce TRAIL expression,

also crosstalk of these signaling pathways is found. This is evidenced by p38MAPK-mediated type I IFN production ([32, 33], data not shown), which may explain our findings that p38MAPK induces TRAIL independently of NAB2. In addition, PI3K signaling induces IRF-7 translocation to the nucleus in activated pre-pDCs [34], a process required for type I IFN production. However, we found a mere 50% reduction of the IFN-β burst in CAL-1 cells upon PI3K block,

while TRAIL induction was fully abrogated (Fig. 4B and E and Supporting Information Fig. 5D). Therefore, our data point to PI3K-NAB2 activation being the dominant regulatory pathway for TRAIL induction directly Doxorubicin clinical trial downstream of TLR triggering. Whether IRF-7 translocation regulates also the induction of NAB2 in addition to type I IFN, or whether their induction occurs independently but in parallel downstream of PI3K signaling, remains to be determined. We found that PI3K signaling induces NAB2 upon TLR triggering, but does so independently of mTOR. Which downstream targets of PI3K govern NAB2 induction is to date unresolved. Potential targets of PI3K activity Lck are the NAB2 binding partners EGR-1, 2, and 3 that mediate NAB2 transcription as part of their feedback loop [27]. We are currently investigating this

possibility. Interestingly, NAB2 induces TRAIL expression in human pDCs, but suppresses TRAIL induction in murine CD8+ T cells [21]. This apparent divergence of NAB2 activity was also found in other cell types and has been attributed to different cell lineages [27]. It is therefore of interest to compare NAB2 activity in pDCs with lymphoid cells such as B cells and NK cells. Our preliminary studies indeed point to such cell lineage specificity, and indicate that basal mRNA levels of EGR-1, 2, and 3 — the binding partners of NAB2 — vary between different cell lineages (M. Balzarolo and M.C. Wolkers, unpublished observations). Provided that the EGR proteins can have both stimulatory (EGR-1) and pro-apoptotic (EGR-2/3) functions [19], this differential expression profile of EGR genes could result in the differential transcription activity of NAB2. Alternatively, it has been shown that the co-activatory versus corepressive action of NAB2 is dictated by the affinity of the EGR target genes to the promoter region, which depends on conserved (= high affinity and co-repressive) versus nonconserved (=low affinity and co-activatory) EGR-binding sites [35].

As shown in Fig. 1C, rPer a 1.0101 protein reacted to 80% (12 of 15) of the sera from cockroach allergy patients, while rPer a 1.0104 reacted to 73.3% (11 of 15) of the sera. Among the cockroach allergy patients, eight reacted to both rPer a 1.0101 and rPer a 1.0104. Both allergens did not react to the sera from 6 ragweed allergic patients and four HC. Other proteins of E. coli BL21 (DE3) did not react to the sera from cockroach Dabrafenib allergic patients (data not shown). It has been reported that German cockroach extract can activate PAR-2 [7] and that

rPer a 7 can upregulate the expression of PARs on P815 cells [8]. We therefore anticipate that rPer a 1.01 may also affect the expression of PARs on P815 cells. As expected, real-time PCR showed that rPer a 1.0101 and rPer a 1.0104 upregulated mRNA expression of PAR-1 in P815 cells at 6 h following incubation (Fig. 2A). rPer a 1.0101 and rPer a 1.0104 induced also an upregulated expression of PAR-2 (Fig. 2B) and PAR-3 (Fig. 2C) mRNAs in P815 cells. Similarly, both rPer a 1.0101 and rPer a 1.0104 elicited concentration-dependent increase in PAR-4 mRNA

expression, which started at 2 h Olaparib and reached the peak value at 6 h following incubation (Fig. 2D). Specific antibody against rPer a 1.01 blocked the rPer a 1.0101- and rPer a 1.0104-induced expression of PAR mRNAs by approximately up to 78.4% and 82.1%. To confirm influence of rPer a 1.0101 or rPer a 1.0104 on the expression of PAR proteins, immunofluorescent microscopy and flow cytometry analyses were applied. Immunofluorescent microscopy showed that rPer a 1.0101 induced an upregulated expression of PAR-1 and PAR-2, whereas rPer a 1.0104 provoked

an enhanced expression Guanylate cyclase 2C of PAR-1 and PAR-4 in P815 cells (Fig. 3A). The more detailed study with flow cytometry analysis (Fig. 3B) revealed that minimum of 1.0 μg/ml of rPer a 1.0101 or rPer a 1.0104 was required to induce significantly enhanced expression of PAR-1 or PAR-4 proteins, respectively. rPer a 1.0101 at 0.1 and 1.0 μg/ml provoked also enhanced PAR-2 expression by up to 2.5-fold (Fig. 3C). The time course study showed that rPer a 1.0101 and rPer a 1.0104 induced upregulation of expression of PARs initiated at 2 h and continuously increased until 16 h following incubation (Fig. 3D). Specific antibody against rPer a 1.01 blocked the rPer a 1.0101 induced expression of PAR-1 and PAR-2 by approximately 74.6% and 77.2%, and rPer a 1.0104 induced the expression of PAR-1 and PAR-4 by approximately up to 72.5% and 80.1%, respectively. Calcium ionophore A23187 (100 ng/ml) had little effect on the expression of PARs on P815 cells following 2-, 6- and 16-h incubation (data not shown). It has been recognized that cytokines such as Th2 cytokines play a key role in the pathogenesis of allergic inflammation and that mast cells are one of major sources of cytokines.

4B). Mice immunized with GFP+ CD8α+ cDCs from non-protected mice had equivalent bacterial titers as non-transferred animals upon challenge infection. In fact, only GFP+ CD8α+ cDCs from mice immunized with the protective dose of secA2−Lm were

able to induce substantial levels of immunity. Since the number of bacteria per infected cell is the same between the two conditions of immunization, it suggested that other signals distinct from those given by cytosolic bacteria are allowing CD8α+ cDCs from protected animals to be optimally conditioned to induce CD8+ T-cell protective memory. Protected mice were immunized with ten-fold more bacteria than non-protected learn more animals, likely leading to a stronger inflammatory environment at the time of DC maturation. To provide support for this hypothesis, we measured the early inflammatory environment (5 h) under Palbociclib research buy the two conditions of immunization (Fig. 5). As proposed, we readily detected a strong inflammatory response

that included cytokines and chemokines involved in DC maturation in mice that received 107secA2−Lm. Animals injected with the lower numbers of bacteria were comparable to non-immunized control groups and exhibited low levels of inflammation. We next sought to determine whether this finding held true for animals immunized with other well-established Cediranib (AZD2171) protective Lm immunizations, e.g. wt Lm or the attenuated mutant actA−Lm25 (Supporting Information Fig. 5) and monitored several inflammatory mediators (IL-1β, CCL2, IL-12p70 and TNF-α) over a 48 h kinetics. In all groups that received protective immunization (e.g. 107secA2 Lm−, 106actA−Lm

and 3000 wt Lm), inflammation reached levels that were never measured in mice immunized with the non-protective dose of secA2−Lm. In the case of wt Lm immunization, however, such levels of inflammation were only observed at later time points (24–48 h), a result in agreement with former studies 26, which also correlates with the low initial inocula and the growth kinetics of wt Lm in vivo 16. Therefore, collectively these data favor the idea that during a protective immunization, CD8α+ cDCs receive stronger extracellular inflammatory signals than during non-protective immunization, which likely contribute to their optimal maturation in vivo. To further support to our interpretation that both cytosolically delivered and extracellular signals are conditioning CD8α+ cDC optimal programming, we compared the maturation profiles of infected and non-infected CD8α+ cDCs from mice immunized with the two doses of secA2−Lm.

82 We then demonstrated that RTP4 was also expressed in the uterine endometrium, which was surprising because expression of this gene was initially thought to be confined to olfactory neurons. Furthermore, in vitro treatment with IFN-τ increased RTP4 expression by a cell line derived from the uterine glandular

epithelium.82 It is not difficult to imagine potential roles for a chemosensory receptor transporting protein in the uterus during early pregnancy because chemokines are proposed to aid in trophoblast attachment and invasion.36 The chemokine CXCL10 was upregulated in the endometrium of pregnant ewes, learn more and the receptor (CXCR3) was localized to the trophectoderm.83 Moreover, chemotaxis assays demonstrated that CXCL10 regulates migration and/or distribution of PBMC in the uterus during early pregnancy. Perhaps RTP4 affects chemokine receptors during early pregnancy to recruit immune cells to the pregnant endometrium.84 Further studies are needed to determine the role(s) of RTP4 in the endometrium during early pregnancy. What this experiment did reveal, however, was that gene expression in PBL during early pregnancy provided a novel and non-invasive mechanism to

identify new genes regulated in the uterus during early pregnancy. We hypothesize that by profiling gene expression patterns in PBL, we may be able to identify expression patterns associated with successful and unsuccessfully pregnancy outcome. By virtue of Paclitaxel the differences in placental structure check details and hormonal signaling from the conceptus, it is likely that early pregnancy in cattle and humans present some very unique challenges for the maternal immune system. However, examination of immune responses to early pregnancy in these species does suggest there are some similarities. This is especially the case during the very early stages of embryo development in the uterus prior to the formation of a functioning hemochorial placenta. During this stage of pregnancy, blastocysts of both species are dependent upon uterine secretions for nutrition, they both

must attach to the endometrial epithelium, and they first encounter the endometrial mucosal immune system. The idea that early pregnancy in humans and ruminants may share more similarities than later pregnancy is supported by the elegant work of Knox and Baker18 showing that genes involved in early placental development are evolutionarily ancient compared to those involved in mature placental function. Figure 1 illustrates that early conceptus-immune interactions occur on a background of a progesterone-primed endometrium that exhibits selective immunosuppression. Conceptuses of both species secrete factors that extend the lifespan of the CL, and these factors affect immune cell function in the endometrium and in the peripheral blood.

36 A third study provides level IV evidence that weight loss appears to be associated with a fall in total cholesterol in kidney transplant recipients.37 The recommendation that a diet rich in wholegrain, low glycaemic index and high fibre carbohydrates as well as rich sources of vitamin E and monounsaturated fat should be followed by adult kidney transplant recipients with elevated serum total cholesterol, LDL-cholesterol and triglycerides, is based on evidence from the following three studies: Stachowska et al.34

investigated the effect www.selleckchem.com/products/PLX-4032.html of a modified Mediterranean diet on serum lipid levels in a single-centre, randomized controlled study. Adult kidney transplant recipients with stable graft function were randomized to receive one of two diets for a 6-month period: Treatment: Modified Mediterranean diet (n = 21; 15 males, six females), containing carbohydrates with a low glycaemic index (amylose-poor, cellulose-rich), 30 mL cold-pressed olive oil with only rapeseed oil used find more in cooking, foods rich in alpha-tocopherol (including nuts, grains and linseeds), fresh vegetables with each meal and

daily animal protein of 35–50 g for males and 23–46 g for females. Energy intake was attributed as follows: 47% carbohydrates, 38% fat, 15% protein. Immunosuppressive and antihypertensive regimens were not changed and no antilipemic medications were administered before or during the study out period. Dietary compliance of subjects in both groups was assessed every 4 weeks by means of 24 h food diaries and by monitoring oleic acid content of plasma triglycerides. In the treatment group, total cholesterol dropped from 230 to 210 mg/dL, or 5.9–5.4 mmol/L (P < 0.02) and triglycerides dropped from 194 to 152 mg/dL, or 2.5–1.7 mmol/L (P < 0.0007). Neither total cholesterol nor triglycerides dropped in the control group. There was no significant difference between the groups with respect to weight, body mass index and body fat levels at the

start or the end of the study period. The key limitations of this study are: the small sample size; and The study provides level III-3 evidence that a modified Mediterranean diet can be effective in lowering total cholesterol and triglycerides. The results of this study concur with the findings of studies in non-transplant populations.34 Shen et al.35 conducted a pseudo-randomized controlled study examining the effect of diet on serum lipids. They designed a diet containing less than 500 mg cholesterol, less than 35% calories from fat, less than 50% calories from carbohydrate, polyunsaturated to saturated fat ratio greater than 1, limited alcohol intake. A sodium restriction was made if the transplant recipient had hypertension.

However,

it is not clear how the loss of TDP-43 results in cell dysfunction or cell loss. TDP-43 was first identified as a protein that binds to DNA, and it is now considered to regulate RNA metabolism.[17] Using a method that identifies the mRNA binding to a specific protein, find more many RNAs that might be regulated by TDP-43 have been identified.[18, 19] These studies have shown that TDP-43 binds to long mRNA molecules with large introns and regulates the splicing and amounts of mRNA in several ways.[18, 19] Consequently, the depletion of TDP-43 might alter pre-mRNA metabolism. Indeed, the alteration of RNA profiles has been reported from cultured cells and model animals with depleted TDP-43. In ALS, alterations of mRNA expression profiles have been reported,[20-22] although the association between TDP-43 and these alterations of mRNA observed in ALS remain to be clarified. To our knowledge, POLDIP3 is the only gene in which the splicing is directly regulated by TDP-43 and is altered in spinal motor

neurons with ALS but not in brain with frontotemporal lobar degeneration.[23, 24] In addition, immunohisotochemical analysis indicated that several genes Erlotinib research buy processed by TDP-43 express key molecules for function or survival of spinal motor neurons and show decreasing amounts of products.[25] However, it is unclear how the function of TDP-43 correlates with the depletion of these products. Thus, the specific functions of TDP-43 have not been fully evaluated in vitro or in ALS patients. These disturbances of RNA metabolism might not be explained simply by the

loss of TDP-43 function on pre-mRNA. Therefore, some researchers have speculated that TDP-43 serves another function associated with RNA metabolism.[26] TDP-43 forms foci in the nucleus and associates with several nuclear bodies, suggesting that TDP-43 plays a role in L-gulonolactone oxidase the functioning of nuclear bodies. Nuclear bodies are classified and identified by their unique protein components.[27] In addition, most of these bodies are tightly associated with a unique RNA and regulate that particular RNA metabolism.[28, 29] In contrast to cytoplasmic organelles, nuclear bodies do not have a membranous structure that separates their contents from nucleoplasm. Thus, the components of nuclear bodies are frequently exchanged between the bodies and the nucleoplasm. The dynamism of the components is a unique characteristic of nuclear bodies. The protein components decrease their mobility in nuclear bodies as compared to that in nucleoplasm. Thus, the bodies are recognized based on the increased concentration of the component protein. The nucleolus and Cajal bodies are the most well-known nuclear bodies. The nucleolus is the center for maturation of rRNA, whereas Cajal bodies are sites for the maturation of U snRNAs and consist of coilin.

We found that the surface protein A (SasA) of S. aureus could protect mice from lethal challenge of the bacteria. Staphylococcus aureus, a conditional pathogenic Gram-positive bacterium, is the leading cause of bloodstream, lower respiratory tract and skin/soft-tissue infections, accounting for 20–25% of all nosocomial infections (1,2,3). Bacteremia is the most prevalent type of S. aureus infections in hospitalized patients, followed by lower respiratory tract infections and skin/soft tissue infections (4,5). S. aureus is able

to adapt to new antibiotics and acquire antibiotic resistance (6). The extensive use of antibiotics has resulted in increased resistance among S. aureus clinical isolates. In patients with large area burn, it was found that more than 90% of S. aureus isolates were resistant to 11 types of antibiotics, including ampicillin, cefazolin, ciprofloxacin, gentamicin, levofloxacin, clidamycin, erythromycin, oxacillin, penicillin(16). https://www.selleckchem.com/products/Dasatinib.html Due to multi-drug resistance and the ability to 3-deazaneplanocin A concentration acquire resistance to new antibiotics quickly, it is more and more difficult to treat S. aureus infection, especially with the emergence of vancomycin resistant S. aureus strains (7,8). As a result, many investigators resort to immunological approaches to contain S. aureus infection (9). Many components of S. aureus, such as capsular polysaccharide (9), poly-N-acetylglucosamine

(10), clumping factor A (11), clumping factor B (12), iron-regulated surface determinant (IsdB) (13) and fibronectin-binding protein (FnBP) (14), can generate immune responses that afford partial protection against S. aureus challenge in experiment animals. It is difficult to develop S. aureus vaccines because there are many pathogenic determinants in S. aureus and different clinical isolates may have different pathogenic determinants. Ideal vaccine candidates for S. aureus should be expressed broadly in different S. aureus

clinical isolates and be consistent among different strains. Vaccines consisting of several components may induce better protective immunity against infective Pyruvate dehydrogenase S. aureus (15). In this study, to screen good vaccine candidates against S. aureus, a panel of pathogenic proteins of S. aureus was expressed and dot blotted with sera from mice infected with S. aureus USA300, 546 and 1884, respectively. The proteins that interact with the sera were selected to immunize BALB/c mice. The immunized mice were then challenged with S. aureus USA300. A protein named SasA was found to be able to induce protective immunity against lethal challenge of S. aureus USA300. Staphylococci were cultured on tryptic soy agar or in broth at 37 °C. S. aureus USA300 were obtained from ATCC. This strain does not produce toxic shock syndrome toxin. The lethal dosage of S. aureus USA300 or S. aureus 546 was determined before as in respectively. S. aureus 546 and S. aureus 1884 were obtained from China Veterinary Culture Collection Center (CVCC). E.

NKRs were first described as surface receptors on NK cells that bind to specific HLA class I molecules (4). Upon binding to their respective ligands, the receptors transmit inhibitory or activating intracellular signals. Many of these inhibitory and activating receptors have been identified. NKG2D, NKG2A, and KIR3DL1 are three of ZD1839 in vivo the most prevalent NKRs and play important roles in a variety of cellular functions (5). NKG2D and NKG2A are both members of the C-type

lectin NKR family. NKG2D is a key member of an array of receptors that can activate or co-stimulate NK cells, while NKG2A recognizes non-classical HLA-E molecules and inhibits the function of NK cells (6–7). Meanwhile, KIR3DL1 is one of the KIRs from the immunoglobulin-like superfamily. This BKM120 receptor binds to HLA-B and HLA-A allotypes bearing the HLA-Bw4 serospecificity and delivers inhibitory signals (8). Since their discovery on NK cells, NKR expression has also been detected on T cells. Although both CD4+ and CD8+αβT cells can express NKRs, expression is much more common on CD8+αβ T cells (9–10). These NKRs have been shown to be functional. Certain NKRs are able to downmodulate cytotoxicity induced by TCR/CD3, and cross-linking of NKRs may inhibit cytolysis by CD8+ T cells (3). Additionally,

TCR-initiated stimulatory signals can be overridden by signals generated by inhibitory NKRs, preventing T cell cytokine release (11). In contrast, NKG2D is an activating receptor that is expressed on CD8+ T cells and some CD4+ T cells Dichloromethane dehalogenase (12). NKG2D is a potent costimulator of TCR-mediated functions that up-regulates antigen-specific, T cell-mediated cytotoxicity directed against cells or tissues expressing stress-induced NKG2D ligands, particularly under conditions of suboptimal TCR engagement (13–14). In addition, NKG2D on T cells can function

independently of the TCR (14). Only a few studies have been published on the expression of NKRs on T cells in HIV infection. One research group found that HIV-specific CTL isolated from infected patients were inhibited in their cytolytic activity against HIV-expressing autologous target cells as a consequence of the surface expression of iNKR. Furthermore, addition of anti-NKR mAbs restored CTL cytolytic activity (15). This finding strongly suggests that iNKRs are involved in the downregulation of HIV-specific CTL activity. Consistent with this, coexpression of multiple iNKRs on CD8+ T cell clones derived from HIV-infected patients has been observed (16). Another study observed low expression of inhibitory NKRs on CD8+ T cells in HIV-infected, long-term non-progressors, indicating that a lack of iNKR-mediated functional inhibition may provide an additional mechanism of efficient control of viral spread in LTNPs (17). Moreover, the expression of NKG2D on NK cells was lower in HIV-infected patients (18).