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.

Keywords: influenza virus; innate immunity; monocytes; plasmacytoid dendritic cells; pregnancy.

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Figures

Figure 1.

Monocyte and plasmacytoid dendritic cell (pDC) frequency and rate of infection with A/California/7/2009 (pH1N1) and A/Victoria/361/2011 (H3N2) influenza A virus in pregnant (P) and nonpregnant (NP) women. Peripheral blood mononuclear cells (PBMCs) from women in the NP (black dots) and P (gray dots) groups were infected with pH1N1 or H3N2 influenza A virus at a multiplicity of infection of 3 for 7 hours or were mock infected (NS). A, Cohort demographic characteristics. B, Frequency of monocytes and pDCs. C, Frequency of influenza virus nucleoprotein (NP)–positive monocytes and pDCs, respectively, as detected by intracellular staining. Each dot represents the cell frequency from 1 patient. Bars represent the mean of each population. *P < .05, ***P < .001, and ****P < .0001 for differences between the P and NP groups.

Figure 2.

Monocyte and plasmacytoid dendritic cell (pDC) immune responses to A/California/7/2009 (pH1N1) and A/Victoria/361/2011 (H3N2) influenza A virus infection in pregnant (P) and nonpregnant (NP) women. Peripheral blood mononuclear cells (PBMCs) from women in the NP (black dots) and P (gray dots) groups were infected with pH1N1 or H3N2 influenza A virus at a multiplicity of infection of 3 for 7 hours or were mock infected (NS). A, Frequency of CD69-expressing monocytes (left) and pDCs (right). B, Frequency of HLA-DR expression on monocytes and pDCs. C and D, Frequency of monocytes and pDCs producing interferon γ–induced protein 10 (IP-10) and macrophage inflammatory protein 1β (MIP-1β), respectively. Each dots represents the cell frequency for 1 patient. *P < .05, **P < .01, ***P < .001, and ****P < .0001 for differences between the P and NP groups.