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The secretion of IL-22 from mucosal NKp44⁺ NK cells is associated with microbial translocation and virus infection in SIV/SHIV-infected Chinese macaques.

Wang W, Wu F, Cong Z, Liu K, Qin C, Wei Q - J Immunol Res (2014)

Bottom Line: Microbial translocation (MT) causes systemic immune activation in chronic human immunodeficiency virus (HIV) infection.As a result, the degranulation capacity and IL-22 production of mucosal NKp44(+) NK cells were associated with the MT level in the SHIV-infected macaques.The number of mucosal NKp44(+) NK cells and interleukin-22 (IL-22) secretion by these cells increased before MT occurred.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Key Laboratory of Human Diseases Animal Models, State Administration of Traditional Chinese Medicine, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medical Center, Peking Union Medical College, No. 5 Panjiayuan Nanli, Chaoyang District, Beijing 100021, China.

ABSTRACT
Microbial translocation (MT) causes systemic immune activation in chronic human immunodeficiency virus (HIV) infection. The role of a novel subtype of innate lymphoid cells, the NKp44(+) NK cells, in HIV/simian immunodeficiency virus- (SIV-) induced MT remains unknown. In this study, 12 simian-human immunodeficiency virus- (SHIV-) infected macaques were chosen and split into two groups based on the MT level. Blood and Peripheral lymphoid tissue were sampled for flow cytometric analysis, viral load detection, and interleukin testing. Then, six naive Chinese macaques were used to determine the dynamics of cytokine secretion from mucosal NKp44(+) NK cells in different phases of SIV infection. As a result, the degranulation capacity and IL-22 production of mucosal NKp44(+) NK cells were associated with the MT level in the SHIV-infected macaques. And the number of mucosal NKp44(+) NK cells and IL-22 secretion by these cells were lower in the chronic phase than in the early acute phase of SIV infection. The number of mucosal NKp44(+) NK cells and interleukin-22 (IL-22) secretion by these cells increased before MT occurred. Therefore, we conclude that a decline in IL-22 production from mucosal NKp44(+) NK cells induced by virus infection may be one of the causes of microbial translocation in HIV/SIV infection.

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Related in: MedlinePlus

Numerical, phenotypical, and functional analyses of natural killer (NK) cells and the subtypes of different tissues from the microbial translocation (MT)high and MTlow groups. (a) Distribution of macaque NK cell subsets in blood and tissues from the MThigh and MTlow groups. (b) NK cell subtype in Peyer's patches mononuclear cells (PPMCs) of the MThigh and MTlow groups. (c) Expression of CD69 and (d) CD107a molecules on CD56+ NK cell subsets of the MThigh and MTlow groups. The column bar indicates the mean of the ratio of target cells (mononuclear cells in (a); NK cells in (b); CD56+CD16− NK cells in (c) and (d)). Error bars and individual standard deviations (SD) are shown. *P ≤ 0.05 and **P ≤ 0.01 as calculated by two-sided nonparametric Mann-Whitney U test.
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fig3: Numerical, phenotypical, and functional analyses of natural killer (NK) cells and the subtypes of different tissues from the microbial translocation (MT)high and MTlow groups. (a) Distribution of macaque NK cell subsets in blood and tissues from the MThigh and MTlow groups. (b) NK cell subtype in Peyer's patches mononuclear cells (PPMCs) of the MThigh and MTlow groups. (c) Expression of CD69 and (d) CD107a molecules on CD56+ NK cell subsets of the MThigh and MTlow groups. The column bar indicates the mean of the ratio of target cells (mononuclear cells in (a); NK cells in (b); CD56+CD16− NK cells in (c) and (d)). Error bars and individual standard deviations (SD) are shown. *P ≤ 0.05 and **P ≤ 0.01 as calculated by two-sided nonparametric Mann-Whitney U test.

Mentions: Many lines of evidence have suggested that NK cells contribute to control of HIV/SIV infection [15, 22]. To assess the relationship between MT and NK cells, we determined the frequency of NK cells and the subtypes of PBMCs, lymph node mononuclear cells (LNMCs), PPMCs, and lamina propria mononuclear cells (LPMCs) from the MThigh (n = 6) and MTlow (n = 6) groups of Chinese macaques. Representative results from the gating strategy used to identify NK cell subtypes in PBMCs are shown in Figure  S2(b). The distribution of NK cells was perturbed in different tissues of SHIV-infected Chinese macaques, with the fraction being higher in PBMCs and lower in LNMCs (Figure 3(a)). The frequency of NK cells in PPMCs was higher in the MThigh group than in the MTlow group (P < 0.05) (Figure 3(a)). Analysis of the mucosal NK cell subpopulations using the CD16 and CD56 markers showed that in PPMCs the frequency of CD56+CD16− cells was higher in the MThigh group (P < 0.05) (Figure 3(b)). Analysis of the function of NK subtypes showed that CD69 expression of CD56+CD16− cells of PPMCs in MThigh and MTlow groups was similar (Figure 3(c)), but that the CD107 expression of CD56+CD16− cells of PPMCs in the MThigh group was remarkably higher than in the MTlow group (P < 0.01) (Figure 3(d)), suggesting that the cells in the MThigh group had increased cytolytic function. Furthermore, the CD107 expression of CD56+CD16− cells in the LNMCs was remarkably higher in the MThigh group than in the MTlow group (P < 0.01) (Figure 3(d)), suggesting that NK cells at the immune effector site had increased cytolytic function in the presence of MT.


The secretion of IL-22 from mucosal NKp44⁺ NK cells is associated with microbial translocation and virus infection in SIV/SHIV-infected Chinese macaques.

Wang W, Wu F, Cong Z, Liu K, Qin C, Wei Q - J Immunol Res (2014)

Numerical, phenotypical, and functional analyses of natural killer (NK) cells and the subtypes of different tissues from the microbial translocation (MT)high and MTlow groups. (a) Distribution of macaque NK cell subsets in blood and tissues from the MThigh and MTlow groups. (b) NK cell subtype in Peyer's patches mononuclear cells (PPMCs) of the MThigh and MTlow groups. (c) Expression of CD69 and (d) CD107a molecules on CD56+ NK cell subsets of the MThigh and MTlow groups. The column bar indicates the mean of the ratio of target cells (mononuclear cells in (a); NK cells in (b); CD56+CD16− NK cells in (c) and (d)). Error bars and individual standard deviations (SD) are shown. *P ≤ 0.05 and **P ≤ 0.01 as calculated by two-sided nonparametric Mann-Whitney U test.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4352435&req=5

fig3: Numerical, phenotypical, and functional analyses of natural killer (NK) cells and the subtypes of different tissues from the microbial translocation (MT)high and MTlow groups. (a) Distribution of macaque NK cell subsets in blood and tissues from the MThigh and MTlow groups. (b) NK cell subtype in Peyer's patches mononuclear cells (PPMCs) of the MThigh and MTlow groups. (c) Expression of CD69 and (d) CD107a molecules on CD56+ NK cell subsets of the MThigh and MTlow groups. The column bar indicates the mean of the ratio of target cells (mononuclear cells in (a); NK cells in (b); CD56+CD16− NK cells in (c) and (d)). Error bars and individual standard deviations (SD) are shown. *P ≤ 0.05 and **P ≤ 0.01 as calculated by two-sided nonparametric Mann-Whitney U test.
Mentions: Many lines of evidence have suggested that NK cells contribute to control of HIV/SIV infection [15, 22]. To assess the relationship between MT and NK cells, we determined the frequency of NK cells and the subtypes of PBMCs, lymph node mononuclear cells (LNMCs), PPMCs, and lamina propria mononuclear cells (LPMCs) from the MThigh (n = 6) and MTlow (n = 6) groups of Chinese macaques. Representative results from the gating strategy used to identify NK cell subtypes in PBMCs are shown in Figure  S2(b). The distribution of NK cells was perturbed in different tissues of SHIV-infected Chinese macaques, with the fraction being higher in PBMCs and lower in LNMCs (Figure 3(a)). The frequency of NK cells in PPMCs was higher in the MThigh group than in the MTlow group (P < 0.05) (Figure 3(a)). Analysis of the mucosal NK cell subpopulations using the CD16 and CD56 markers showed that in PPMCs the frequency of CD56+CD16− cells was higher in the MThigh group (P < 0.05) (Figure 3(b)). Analysis of the function of NK subtypes showed that CD69 expression of CD56+CD16− cells of PPMCs in MThigh and MTlow groups was similar (Figure 3(c)), but that the CD107 expression of CD56+CD16− cells of PPMCs in the MThigh group was remarkably higher than in the MTlow group (P < 0.01) (Figure 3(d)), suggesting that the cells in the MThigh group had increased cytolytic function. Furthermore, the CD107 expression of CD56+CD16− cells in the LNMCs was remarkably higher in the MThigh group than in the MTlow group (P < 0.01) (Figure 3(d)), suggesting that NK cells at the immune effector site had increased cytolytic function in the presence of MT.

Bottom Line: Microbial translocation (MT) causes systemic immune activation in chronic human immunodeficiency virus (HIV) infection.As a result, the degranulation capacity and IL-22 production of mucosal NKp44(+) NK cells were associated with the MT level in the SHIV-infected macaques.The number of mucosal NKp44(+) NK cells and interleukin-22 (IL-22) secretion by these cells increased before MT occurred.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health, Key Laboratory of Human Diseases Animal Models, State Administration of Traditional Chinese Medicine, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medical Center, Peking Union Medical College, No. 5 Panjiayuan Nanli, Chaoyang District, Beijing 100021, China.

ABSTRACT
Microbial translocation (MT) causes systemic immune activation in chronic human immunodeficiency virus (HIV) infection. The role of a novel subtype of innate lymphoid cells, the NKp44(+) NK cells, in HIV/simian immunodeficiency virus- (SIV-) induced MT remains unknown. In this study, 12 simian-human immunodeficiency virus- (SHIV-) infected macaques were chosen and split into two groups based on the MT level. Blood and Peripheral lymphoid tissue were sampled for flow cytometric analysis, viral load detection, and interleukin testing. Then, six naive Chinese macaques were used to determine the dynamics of cytokine secretion from mucosal NKp44(+) NK cells in different phases of SIV infection. As a result, the degranulation capacity and IL-22 production of mucosal NKp44(+) NK cells were associated with the MT level in the SHIV-infected macaques. And the number of mucosal NKp44(+) NK cells and IL-22 secretion by these cells were lower in the chronic phase than in the early acute phase of SIV infection. The number of mucosal NKp44(+) NK cells and interleukin-22 (IL-22) secretion by these cells increased before MT occurred. Therefore, we conclude that a decline in IL-22 production from mucosal NKp44(+) NK cells induced by virus infection may be one of the causes of microbial translocation in HIV/SIV infection.

Show MeSH
Related in: MedlinePlus