Effects of pregnancy-associated Listeria monocytogenes infection: necrotizing hepatitis due to impaired maternal immune response and significantly increased abortion rate

Abstract

The impact of L. monocytogenes infection on maternal immune responses as well as on the outcome of pregnancy was studied in a murine model of pregnancy-associated listeriosis. Mice infected i.v. with L. monocytogenes at day 15 of pregnancy showed a significantly impaired bacterial elimination, which resulted in a severe necrotizing hemorrhagic hepatitis. The aggravated course of the infection could be attributed to a suppressed transcription and production of anti-listerial, pro-inflammatory cytokines and chemokines, namely interferon-gamma, tumor necrosis factor, interleukin-12p40, inducible nitric oxide synthase, murine monokine induced by interferon-gamma, and interferon-gamma-inducible protein-10. In addition, listeriosis significantly increased the abortion rate. Infection of the placenta and fetuses was characterized by placental and fetal necrosis with unrestricted bacterial multiplication. A weak transcription of anti-listerial cytokines in the placenta in the absence of a cellular immune response could not prevent the fatal outcome of pregnancy-associated listeriosis.

Complications of Pregnancy and Transplacental Transmission of Relapsing‐Fever Borreliosis

“…During pregnancy, immunological competence is altered to prevent rejection of the fetus. Several diseases-for instance, listeriosis [35] and malaria [36]-are more severe during pregnancy. It is tempting to assume that pregnancy would also lead to increased susceptibility to infection and more-severe disease in RF.…”

Protective Role of Heme Oxygenase-1 in Listeria monocytogenes-Induced Abortion

“…L. monocytogenes infection causes abortion in pregnant mice [23]. However, the factors involved in abortion induced by L. monocytogenes infection in these animals remain unknown.…”

Murine model of pregnancy-associatedListeria monocytogenesinfection

“…The impairment of T cell‐mediated immune response was evident in pregnant mice from the depressed IFN‐γ generating capacity. Serum IFN‐γ levels of infected pregnant mice were significantly reduced in comparison to infected virgin animals [34]. On the contrary, IL‐10 levels increased in the serum of L. monocytogenes infected pregnant mice up to day 3 post infection (p.i.…”

“…), and declined thereafter, being significantly higher at days 3 and 6 p.i. as compared to infected virgin mice [34]. Elevated serum levels of IL‐10 in pregnant mice may contribute to the failure of the maternal anti‐listerial immune response since IL‐10 is known to be involved in down‐regulating protective immune responses by inhibiting Th1 cell differentiation or by blocking cytokine‐induced macrophage activation [35].…”