By Dean L. Winslow, MD, FACP, FIDSA

Professor of Medicine, Division of Hospital Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine

Dr. Winslow reports no financial relationships relevant to this field of study.

SYNOPSIS: In pregnant women, monocytes and plasmacytoid dendritic cells (pDCs) exhibit an exaggerated proinflammatory immune response to influenza A virus compared to nonpregnant women.

SOURCE: Le Gars M, Kay AW, Bayless NL, et al. Increased proinflammatory responses of monocytes and plasmacytoid dendritic cells to Influenza A virus infection during pregnancy. J Infect Dis 2016;214:1666-1671.

Twenty-one healthy pregnant women and 21 nonpregnant control subjects were recruited. PBMCs were isolated from whole blood by Ficoll-Hypaque, cryopreserved, thawed, washed, and then infected with either a pH1N1 or H3N2 strain at an MOI of 3. Cells then were stained and analyzed by CyTOF-1 for markers of activation and cytokine production.

Increased expression of CD69+, HLA-DR, IP-10, and MIP-1B was seen following infection of monocytes and pDCs in culture with both strains of flu. Compared to cells from nonpregnant women, cells from pregnant women showed statistically significantly greater expression of these activation markers.

COMMENTARY

In pregnancy, the immune system is challenged to strike a balance between protecting the mother from infection, yet not rejecting the growing fetus. It has been known for at least a century that pregnant women often develop severe influenza and suffer greater morbidity and mortality than other young people do. This study demonstrated both elevation of activation markers and increased cytokine production in cells from pregnant women compared to nonpregnant women when infected with two different strains of influenza A. This study at least partially elucidates the mechanism of innate immune system activation in response to influenza A virus infection in pregnancy and suggests potential avenues for research on therapeutic interventions.

Another paper published earlier in 2016 showed that the intense pro-inflammatory response of the innate immune system may even be severe enough to induce hemophagocytic lymphohistiocytosis (HLH), which often was found at autopsy in fatal cases of influenza virus infection.1 It would be interesting to see if cells obtained from certain subjects in the current study had pro-inflammatory responses that correlated with genetic markers that were seen in 36% of the cases of HLH seen at autopsy in fatal influenza virus infection.

REFERENCE

  1. Schulert GS, Zhang M, Fall N, et al. Whole-exome sequencing reveals mutations in genes linked to hemophagocytic lymphohistiocytosis and macrophage activation syndrome in fatal cases of H1N1 influenza. J Infect Dis 2016;213:1180-1188.