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Increased neutrophil apoptosis in chronically SIV-infected macaques.

Elbim C, Monceaux V, François S, Hurtrel B, Gougerot-Pocidalo MA, Estaquier J - Retrovirology (2009)

Bottom Line: PMN apoptosis was significantly increased in RMs progressing faster to AIDS as compared to non-progressors RMs. Furthermore, the percentage of apoptotic cells correlated with PMN activation state reflected by increased CD11b expression and reactive oxygen species production.Interestingly, whereas inflammatory cytokines IL-8 and IL-1beta prevent in vitro PMN death, the levels of those cytokines were low in RMs progressing towards AIDS.Altogether, increased PMN death during SIV infection is a new pathogenic effect associated with AIDS progression, adding to the long list of markers associated with disruption of defense against infection.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, UMR, Paris, France. carole.elbim@crc.jussieu.fr

ABSTRACT
Polymorphonuclear neutrophils (PMN) from chronically HIV-infected individuals have been reported to be more prone to die. However, although non-human primates models have been extensively used for improving our knowledge on T cell immunity, the impact of SIV-infection on PMN, in relationships with disease severity, has never been assessed. In our study, we demonstrate that PMN from Rhesus macaques (RMs) of Chinese origin chronically infected with the virulent strain SIVmac251 display increased susceptibility to undergo apoptosis as compared to PMN from RMs infected with the non-pathogenic SIVDeltanef strain. PMN apoptosis was significantly increased in RMs progressing faster to AIDS as compared to non-progressors RMs. Furthermore, the percentage of apoptotic cells correlated with PMN activation state reflected by increased CD11b expression and reactive oxygen species production. Interestingly, whereas inflammatory cytokines IL-8 and IL-1beta prevent in vitro PMN death, the levels of those cytokines were low in RMs progressing towards AIDS. Altogether, increased PMN death during SIV infection is a new pathogenic effect associated with AIDS progression, adding to the long list of markers associated with disruption of defense against infection.

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PMN functions during chronic infection of rhesus macaques with the pathogenic SIVmac251 strain or the attenuated SIVΔnef strain. Basal CD11b expression on the PMN surface (A) and basal ROS production (B) were studied in whole blood samples. Results are expressed as Mean Fluorescence Intensity (MFI). Data are reported as means ± SEM. Comparisons were based on ANOVA and Tukey's posthoc test, using Prism 3.0 software. * Significantly different from healthy controls (SIV- group) (p < 0.05); † Significantly different from SIVΔnef macaques (p < 0.05); †† Significantly different from SIV+ SP (p < 0.05).
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Figure 2: PMN functions during chronic infection of rhesus macaques with the pathogenic SIVmac251 strain or the attenuated SIVΔnef strain. Basal CD11b expression on the PMN surface (A) and basal ROS production (B) were studied in whole blood samples. Results are expressed as Mean Fluorescence Intensity (MFI). Data are reported as means ± SEM. Comparisons were based on ANOVA and Tukey's posthoc test, using Prism 3.0 software. * Significantly different from healthy controls (SIV- group) (p < 0.05); † Significantly different from SIVΔnef macaques (p < 0.05); †† Significantly different from SIV+ SP (p < 0.05).

Mentions: Both CD11b expression (Figure 2A) and ROS production (Figure 2B) of resting PMN (maintained at 4°C) were significantly increased in both slow and moderate progressors relative to healthy and SIVΔnef controls. Furthermore, PMN from moderate progressors exhibited increased CD11b expression and ROS production as compared to slow progressors. Interestingly, the percentage of apoptotic cells correlated with basal PMN activation status (ρ = 0.69, p = 0.01 and ρ = 0.71, p = 0.01, for CD11b expression and ROS production, respectively). The consequences of PMN activation generating general oxidative stress molecules might include an increased PMN susceptibility to apoptotic death during the chronic phase of infection [35]. In addition, these results support the idea that increased granulopoiesis in bone marrow leads to a compensatory release of mature PMN. Interestingly, PMN activation has been reported in the bone marrow of chronically SIV-infected macaques [36], contrasting with a defect in bone marrow lymphopoiesis [37,38]. Infact, reciprocal dynamics of the bone marrow lymphocyte and neutrophil populations lead to cellular competition within a developmental niche. In particular, blocking bone marrow lymphopoiesis results in the specific and reciprocal expansion of the granulocytic compartment in bone marrow [39].


Increased neutrophil apoptosis in chronically SIV-infected macaques.

Elbim C, Monceaux V, François S, Hurtrel B, Gougerot-Pocidalo MA, Estaquier J - Retrovirology (2009)

PMN functions during chronic infection of rhesus macaques with the pathogenic SIVmac251 strain or the attenuated SIVΔnef strain. Basal CD11b expression on the PMN surface (A) and basal ROS production (B) were studied in whole blood samples. Results are expressed as Mean Fluorescence Intensity (MFI). Data are reported as means ± SEM. Comparisons were based on ANOVA and Tukey's posthoc test, using Prism 3.0 software. * Significantly different from healthy controls (SIV- group) (p < 0.05); † Significantly different from SIVΔnef macaques (p < 0.05); †† Significantly different from SIV+ SP (p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2667475&req=5

Figure 2: PMN functions during chronic infection of rhesus macaques with the pathogenic SIVmac251 strain or the attenuated SIVΔnef strain. Basal CD11b expression on the PMN surface (A) and basal ROS production (B) were studied in whole blood samples. Results are expressed as Mean Fluorescence Intensity (MFI). Data are reported as means ± SEM. Comparisons were based on ANOVA and Tukey's posthoc test, using Prism 3.0 software. * Significantly different from healthy controls (SIV- group) (p < 0.05); † Significantly different from SIVΔnef macaques (p < 0.05); †† Significantly different from SIV+ SP (p < 0.05).
Mentions: Both CD11b expression (Figure 2A) and ROS production (Figure 2B) of resting PMN (maintained at 4°C) were significantly increased in both slow and moderate progressors relative to healthy and SIVΔnef controls. Furthermore, PMN from moderate progressors exhibited increased CD11b expression and ROS production as compared to slow progressors. Interestingly, the percentage of apoptotic cells correlated with basal PMN activation status (ρ = 0.69, p = 0.01 and ρ = 0.71, p = 0.01, for CD11b expression and ROS production, respectively). The consequences of PMN activation generating general oxidative stress molecules might include an increased PMN susceptibility to apoptotic death during the chronic phase of infection [35]. In addition, these results support the idea that increased granulopoiesis in bone marrow leads to a compensatory release of mature PMN. Interestingly, PMN activation has been reported in the bone marrow of chronically SIV-infected macaques [36], contrasting with a defect in bone marrow lymphopoiesis [37,38]. Infact, reciprocal dynamics of the bone marrow lymphocyte and neutrophil populations lead to cellular competition within a developmental niche. In particular, blocking bone marrow lymphopoiesis results in the specific and reciprocal expansion of the granulocytic compartment in bone marrow [39].

Bottom Line: PMN apoptosis was significantly increased in RMs progressing faster to AIDS as compared to non-progressors RMs. Furthermore, the percentage of apoptotic cells correlated with PMN activation state reflected by increased CD11b expression and reactive oxygen species production.Interestingly, whereas inflammatory cytokines IL-8 and IL-1beta prevent in vitro PMN death, the levels of those cytokines were low in RMs progressing towards AIDS.Altogether, increased PMN death during SIV infection is a new pathogenic effect associated with AIDS progression, adding to the long list of markers associated with disruption of defense against infection.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, UMR, Paris, France. carole.elbim@crc.jussieu.fr

ABSTRACT
Polymorphonuclear neutrophils (PMN) from chronically HIV-infected individuals have been reported to be more prone to die. However, although non-human primates models have been extensively used for improving our knowledge on T cell immunity, the impact of SIV-infection on PMN, in relationships with disease severity, has never been assessed. In our study, we demonstrate that PMN from Rhesus macaques (RMs) of Chinese origin chronically infected with the virulent strain SIVmac251 display increased susceptibility to undergo apoptosis as compared to PMN from RMs infected with the non-pathogenic SIVDeltanef strain. PMN apoptosis was significantly increased in RMs progressing faster to AIDS as compared to non-progressors RMs. Furthermore, the percentage of apoptotic cells correlated with PMN activation state reflected by increased CD11b expression and reactive oxygen species production. Interestingly, whereas inflammatory cytokines IL-8 and IL-1beta prevent in vitro PMN death, the levels of those cytokines were low in RMs progressing towards AIDS. Altogether, increased PMN death during SIV infection is a new pathogenic effect associated with AIDS progression, adding to the long list of markers associated with disruption of defense against infection.

Show MeSH
Related in: MedlinePlus