Plasma levels of α‐defensins 1–3 are an indicator of neutrophil activation in pregnant and post‐partum women

Okazaki, Takayuki; Ota, Yoriko; Yuki, Nobuhiro; Hayashida, Ayako; Shoda, Akiko; Nishikawa, Masayoshi; Oshima, Kyoko; Fukasawa, Ichio; Watanabe, Hiroshi; Inaba, Noriyuki

doi:10.1111/j.1447-0756.2007.00626.x

Cited by 7 publications

(4 citation statements)

References 24 publications

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“…This is not contradictory with our results with MDDC since α-defensins1-3 detected in plasma are mainly secreted by neutrophils[41]. The possible association between plasma levels of α-defensins1-3 and neutrophil activation was not analyzed in our study, but it has been previously found in pregnant and post-partum women [55]. Furthermore, Baroncelli et al [45], reported a marked increased in α-defensins1-3 plasma levels only two weeks after SIV post-infection of macaques, which coincided with the peak of viral replication, but following the acute phase of infection the levels of α-defensins1-3 decreased.…”

Section: Discussioncontrasting

confidence: 78%

Increased α-Defensins 1-3 Production by Dendritic Cells in HIV-Infected Individuals Is Associated with Slower Disease Progression

et al. 2010

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BackgroundDefensins are natural endogenous antimicrobial peptides with potent anti-HIV activity and immuno-modulatory effects. We recently demonstrated that immature dendritic cells (DC) produce α-defensins1-3 and that α-defensins1-3 modulate DC generation and maturation. Since DC-HIV interaction plays a critical role during the first steps of HIV infection, we investigated the possible impact of α-defensins1-3 production by DC on disease progression.Methodology/Principal FindingsMonocyte-derived DC (MDDC) were analyzed comparatively in healthy controls (HC) and HIV-infected patients, including untreated “elite” and “viremic” controllers, untreated viremic non-controllers and antiretroviral-treated patients. We found that production of α-defensins1-3 was significantly increased in MDDC from HIV-infected patients versus HC, and this increase was mainly due to that observed in controllers, while in non-controllers the increase was not statistically significant (controllers vs. HC, p<0.005; controllers vs. non-controllers p<0.05). Secreted α-defensins1-3 by immature MDDC positively correlated with CD4 T cell counts in controllers, but not in non-controllers. Moreover, independently of their clinical classification, HIV-infected patients with higher α-defensins1-3 secretion by immature MDDC showed slower disease progression, measured as no decrease in the number of CD4+ T-cells below 350 cell/mm3, lower increase of plasma viral load and no initiation of treatment over time. Plasma alpha-defensins1-3 levels lacked any relationship with immunologic and virologic parameters.Conclusions/SignificanceHigh production of α-defensins1-3 by immature DCs appears as a host protective factor against progression of HIV-1infection, suggesting potential diagnostic, therapeutic and preventive implications. This protective effect may arise from the activity of α-defensins1-3 to damage the virions prior and/or after their internalization by immature DC, and hence favoring a more efficient viral processing and presentation to HIV-specific CD4+ T cells, without or with a minor rate of transmission of infectious HIV-1 virions.

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Section: Discussioncontrasting

confidence: 78%

Increased α-Defensins 1-3 Production by Dendritic Cells in HIV-Infected Individuals Is Associated with Slower Disease Progression

et al. 2010

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“…Moreover, evidence suggests that elevated levels of α-defensins 1-3 in serum correlated with adverse pregnancy outcomes [43,44]. While we observed a trend towards less α-defensins 1-3 production from DCs collected in the 3 rd trimester relative to those collected from the same patient in the 1 st trimester, the difference was not statistically significant.…”

Section: Discussioncontrasting

confidence: 73%

Alpha-defensins 1-3 release by dendritic cells is reduced by estrogen

Escribese

Rodriguez-García

Sperling

et al. 2011

Reprod Biol Endocrinol

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BackgroundDuring pregnancy the immune system of the mother must protect any activation that may negatively affect the fetus. Changes in susceptibility to infection as well as resolution of some autoimmune disorders represent empirical evidence for pregnancy related alterations in immunity. Sex hormones reach extremely high levels during pregnancy and have been shown to have direct effects on many immune functions including the antiviral response of dendritic cells. Among the immunologically active proteins secreted by monocyte derived DCs (MDDC) are the alpha-defensins 1-3. This family of cationic antimicrobial peptides has a broad spectrum of microbicidal activity and has also been shown to link innate to adaptive immunity by attracting T cells and immature DCs, which are essential for initiating and polarizing the immune response.MethodsWe compare culture-generated monocyte derived DCs (MDDCs) with directly isolated myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) and measure their alpha-defensins 1-3 secretion by ELISA both, in basal situations and after hormone (E2 or PG) treatments. Moreover, using a cohort of pregnant women we isolated mDCs from blood and also measure the levels of these anti-microbial peptides along pregnancy.ResultsWe show that mDCs and pDCs constitutively produce alpha-defensins 1-3 and at much higher levels than MDDCs. Alpha-defensins 1-3 production from mDCs and MDDCs but not pDCs is inhibited by E2. PG does not affect alpha-defensins 1-3 in any of the populations. Moreover, alpha-defensins 1-3 production by mDCs was reduced in the later stages of pregnancy in 40% of the patients.ConclusionsHere, we demonstrate that mDCs and pDCs secrete alpha-defensins 1-3 and present a novel effect of E2 on the secretion of alpha-defensins 1-3 by dendritic cells.

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“…Furthermore, we observed an increase in HPN-1, as it points out that there is an ongoing infection. In fact, it has been shown that an increase in HPN-1 coincides with an increase in neutrophils, which supports the presence of an infectious pathology [ 42 ].…”

Section: Discussionmentioning

confidence: 89%

Diagnostic and Therapeutic Potential for HNP-1, HBD-1 and HBD-4 in Pregnant Women with COVID-19

Brancaccio

Mennitti

Calvanese

et al. 2022

IJMS

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Pregnancy is characterized by significant immunological changes and a cytokine profile, as well as vitamin deficiencies that can cause problems for the correct development of a fetus. Defensins are small antimicrobial peptides that are part of the innate immune system and are involved in several biological activities. Following that, this study aims to compare the levels of various cytokines and to investigate the role of defensins between pregnant women with confirmed COVID-19 infection and pregnant women without any defined risk factor. TNF-α, TGF-β, IL-2 and IL-10, β-defensins, have been evaluated by gene expression in our population. At the same time, by ELISA assay IL-6, IL-8, defensin alpha 1, defensin beta 1 and defensin beta 4 have been measured. The data obtained show that mothers affected by COVID-19 have an increase in pro-inflammatory factors (TNF-α, TGF-β, IL-2, IL-6, IL-8) compared to controls; this increase could generate a sort of “protection of the fetus” from virus attacks. Contemporarily, we have an increase in the anti-inflammatory cytokine IL-10 and an increase in AMPs, which highlights how the mother’s body is responding to the viral attack. These results allow us to hypothesize a mechanism of “trafficking” of antimicrobial peptides from the mother to the fetus that would help the fetus to protect itself from the infection in progress.

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Plasma levels of α‐defensins 1–3 are an indicator of neutrophil activation in pregnant and post‐partum women

Abstract: Our results suggest that there is a positive association between defensin levels and neutrophil activation in pregnant and post-partum women.

Cited by 7 publications

References 24 publications

Increased α-Defensins 1-3 Production by Dendritic Cells in HIV-Infected Individuals Is Associated with Slower Disease Progression

Increased α-Defensins 1-3 Production by Dendritic Cells in HIV-Infected Individuals Is Associated with Slower Disease Progression

Alpha-defensins 1-3 release by dendritic cells is reduced by estrogen

Diagnostic and Therapeutic Potential for HNP-1, HBD-1 and HBD-4 in Pregnant Women with COVID-19

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