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

Abstract

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.

Influenza-Induced Interferon Lambda Response Is Associated With Longer Time to Delivery Among Pregnant Kenyan Women

“…These changes alter immunity to a wide range of pathogens, including influenza virus, which significantly drives morbidity and mortality in the pregnant population. In general, women have enhanced innate NK cell, monocyte, and dendritic cell responses to influenza virus (10,11,13,58), yet there are also reports that there is reduced IFN-alpha and IFN-lambda production in response to influenza (59). In general, adaptive immune function is thought to be suppressed during pregnancy, though pregnant women respond adequately to influenza immunization (9,60).…”

“…Changes in immune function during pregnancy may increase susceptibility to, or complications from, a wide range of infectious diseases (9). Further, pregnancy is not a globally immunosuppressed state; some cell types increase in frequency and function while others have diminished function, both locally and systemically, during pregnancy (8,(10)(11)(12)(13)(14)(15)(16). Thus, it is possible that immune mechanisms play a significant role in driving preterm birth, an idea supported by the fact that many of the known risk factors for preterm birth also alter immune function.…”

Host Factors Affecting Generation of Immunity Against Porcine Epidemic Diarrhea Virus in Pregnant and Lactating Swine and Passive Protection of Neonates

“…Additionally, studies of pregnant women suggest that innate immune cells are actually more responsive to stimuli than in nonpregnant women. In response to influenza antigen, pregnant women have a significantly greater percentage of MIP-1a-producing and polyfunctional NK cells and monocytes and DCs exhibited exaggerated proinflammatory immune responses compared with non-pregnant women [82,83]. Phagocytic activity, α-defensin expression, numbers of neutrophils, monocytes and DCs, and STAT1 signaling are all enhanced during pregnancy in humans, notably in the second and third trimesters [84][85][86].…”

Impact of pregravid obesity on maternal and fetal immunity: Fertile grounds for reprogramming

“…152,154,155 Changes in maternal innate immune responses include increased surface expression of CD11a, CD11b, CD49d, CD14, CD64, and CD54 on monocytes during third trimester. [156][157][158] Moreover, production of proinflammatory cytokines IL-1 , IL-12, IL-6 and oxygen-free radicals following stimulation with LPS or bacteria 152,154,159 as well as responses to viral particles by NK cells, 160 monocytes, 152 and plasmacytoid dendritic (pDC) cells 161 were enhanced with gestation. Although the mechanisms regulating these changes are still unknown, several studies have hypothesized a role for placental microparticles, 162 fetal DNA, 163 and/or maternal metabolic and cytokine changes.…”