Characterizing the Pregnancy Immune Phenotype: Results of the Viral Immunity and Pregnancy (VIP) Study

Kraus, Thomas; Engel, Stephanie M.; Sperling, Rhoda; Kellerman, Lisa; Lo, Yungtai; Wallenstein, Sylvan; Escribese, María M.; Garrido, José; Singh, Tricia; Loubeau, Martine; Moran, Thomas M.

doi:10.1007/s10875-011-9627-2

Cited by 189 publications

(207 citation statements)

References 41 publications

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“…Chemokines are also up-regulated, and systemic leukocytes demonstrate increased chemotactic responsiveness at parturition and perhaps before parturition as well (48,49). In prior studies, stimulation of NK cells from pregnant women with IL-12/IL-15 was not associated with increased levels of MIP-1α or MIP-1β (13,14). However, our own data demonstrate different responses based on the stimulation condition: the increase in MIP-1β production was observed only after infection of PBMC cultures with pH1N1 virus, and less so with H3N2 virus, but not with generalized stimulation with PMA/I.…”

Section: Discussionmentioning

confidence: 95%

“…For instance, suppression of T-cell and natural killer (NK)-cell responses by regulatory T cells during pregnancy is linked to amelioration of certain autoimmune diseases (10)(11)(12). In addition, NK and T cells from pregnant women exhibit decreased interferon (IFN)-γ and macrophage inflammatory protein (MIP)-1β production in response to interleukin (IL)-12/15 stimulation or phorbol 12-myristate 13-acetate and ionomycin (PMA/I) (13)(14)(15)(16). Prior work has also suggested a systemic type 2 T helper (Th2) bias as pregnancy progresses (17,18).…”

mentioning

confidence: 99%

“…Although each of these immune alterations could compromise viral immunity, they are likely an oversimplification because recent longitudinal studies in humans report a complex inflammatory environment during pregnancy, in which both pro-and anti-inflammatory cytokines are increased in concentration (14). Furthermore, increased frequencies of monocytes and dendritic cells were observed whereas NK-cell and T-cell frequencies and functions decreased (13).…”

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confidence: 99%

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Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy

Kay¹,

Fukuyama²,

Aziz

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Pregnant women experience increased morbidity and mortality after influenza infection, for reasons that are not understood. Although some data suggest that natural killer (NK)-and T-cell responses are suppressed during pregnancy, influenza-specific responses have not been previously evaluated. Thus, we analyzed the responses of women that were pregnant (n = 21) versus those that were not (n = 29) immediately before inactivated influenza vaccination (IIV), 7 d after vaccination, and 6 wk postpartum. Expression of CD107a (a marker of cytolysis) and production of IFN-γ and macrophage inflammatory protein (MIP) 1β were assessed by flow cytometry. Pregnant women had a significantly increased percentage of NK cells producing a MIP-1β response to pH1N1 virus compared with nonpregnant women pre-IIV [median, 6.66 vs. 0.90% (P = 0.0149)] and 7 d post-IIV [median, 11.23 vs. 2.81% (P = 0.004)], indicating a heightened chemokine response in pregnant women that was further enhanced by the vaccination. Pregnant women also exhibited significantly increased T-cell production of MIP-1β and polyfunctionality in NK and T cells to pH1N1 virus pre-and post-IIV. NK-and T-cell polyfunctionality was also enhanced in pregnant women in response to the H3N2 viral strain. In contrast, pregnant women had significantly reduced NK-and T-cell responses to phorbol 12-myristate 13-acetate and ionomycin. This type of stimulation led to the conclusion that NK-and T-cell responses during pregnancy are suppressed, but clearly this conclusion is not correct relative to the more biologically relevant assays described here. Robust cellular immune responses to influenza during pregnancy could drive pulmonary inflammation, explaining increased morbidity and mortality.

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Section: Discussionmentioning

confidence: 95%

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confidence: 99%

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Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy

Kay¹,

Fukuyama²,

Aziz

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Of note, several prior studies of influenza immunity during pregnancy, particularly those focused on NK and T cells, studied these cells in isolation and found their responses to be suppressed [3]. Such studies excluded cross-talk with other immune cells.…”

Section: Discussionmentioning

confidence: 99%

“…For example, natural killer (NK) and T cells from pregnant women were deficient in interferon γ (IFN-γ) and macrophage inflammatory protein 1β (MIP-1β) production following cytokine stimulation [3]. However, NK and T cells from pregnant women displayed enhanced IFN-γ and MIP-1β responses to influenza A virus, compared with those from nonpregnant women [4].…”

mentioning

confidence: 99%

Increased Proinflammatory Responses of Monocytes and Plasmacytoid Dendritic Cells to Influenza A Virus Infection During Pregnancy

Gars¹,

Kay²,

Bayless³

et al. 2016

J Infect Dis.

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Pregnancy-induced alterations in immunity may contribute to the increased morbidity associated with influenza A virus infection during pregnancy. We characterized the immune response of monocytes and plasmacytoid dendritic cells ( pDCs) to influenza A virus infection in 21 pregnant and 21 nonpregnant women. In pregnant women, monocytes and pDCs exhibit an exaggerated proinflammatory immune response to 2 strains of influenza A virus, compared with nonpregnant women, characterized by increased expression of major histocompatibility complex class II (approximately 2.0-fold), CD69 (approximately 2.2-fold), interferon γ-induced protein 10 (approximately 2.0-fold), and macrophage inflammatory protein 1β (approximately 1.5-fold). This enhanced innate inflammatory response during pregnancy could contribute to pulmonary inflammation following influenza A virus infection.

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Congenital, Perinatal and Neonatal Infections

2017

Clinical Microbiology for Diagnostic Laboratory Scientists

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Characterizing the Pregnancy Immune Phenotype: Results of the Viral Immunity and Pregnancy (VIP) Study

Abstract: These data show that pregnancy is not a period of immunosuppression but an alteration in immune priorities characterized by a strengthening of innate immune barriers and a concomitant reduction in adaptive/inflammatory immunity in the later stages of pregnancy.

Cited by 189 publications

References 41 publications

Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy

Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy

Increased Proinflammatory Responses of Monocytes and Plasmacytoid Dendritic Cells to Influenza A Virus Infection During Pregnancy

Congenital, Perinatal and Neonatal Infections

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