Influence of pregnancy on the pathogenesis of listeriosis in mice inoculated intragastrically.

Listeria monocytogenes is a gram-positive bacterium that can be isolated from soil, animal feed, water, feces, and tissues from a variety of invertebrate and vertebrate animals, including humans (8). Also, L. monocytogenes is a common contaminant of foodstuffs and has been recovered from raw vegetables, milk products, fish, poultry, and meats at rates of 15 to 70% (11). Consumption of contaminated food products can result in listerial escape from the intestinal lumen and the production of a systemic disease (listeriosis). The most recent listeriosis outbreak resulted in seven deaths and the largest recall of any agricultural product in history (27.4 million pounds of processed meat [3a]). It has been known for some time (26) that cell-mediated immunity is critical in containing and eliminating the infection due, at least in part, to the ability of listeriae to survive intracellularly (reviewed in reference 42). Pregnancy greatly increases the risk of listeriosis in virtually all susceptible animals (14, 24, 41). In humans, approximately 33% of clinically documented cases of listeriosis are in pregnant women (2), and pregnant women constitute approximately 60% of all cases (male and female) in patients aged 10 to 40 years (6). In one outbreak, 65% of those contracting listeriosis were pregnant and 63% of those pregnancies ended in fetal or neonatal death (19). Despite the well-known association of listeriosis with pregnancy, there is incomplete agreement on how pregnancy increases disease risk (5, 45). Laboratory-based investigations have been complicated by the varying virulence of listerial strains (3), the various routes of inoculation employed, and the normal resistance of the preferred host, the mouse, to infection via the natural route, the alimentary tract (22). A better understanding of how pregnancy increases disease risk is critically important in developing prophylactic strategies or, more simply, a scientifically based risk assessment for the exposure of pregnant women to sources of Listeria. Considering that the infectious dose for humans is not known (10, 23) and considering the somewhat arbitrary criteria used to regulate Listeria levels in prepackaged foods (31) and control listeriosis outbreaks (3a), much needs to be done. In this report, we compare the gravid female mouse to her nongravid counterpart with respect to disease severity and susceptibility to infection. Since individual listerial strains differ in their ability to establish an intestinal infection (3), we initially employed two listerial strains, namely, a serotype 4nonb and a serotype 1/2a strain. We found that both strains were completely avirulent in nonpregnant female mice following gavage inoculation and that only the 4nonb strain produced a lethal infection in pregnant animals. The lethality in pregnant animals was not correlated with an increased incidence or level of liver and spleen colonization over that for nonpregnant females but rather with the rate at which embryos and their surrounding decidual covering became infected, suggesting that intrauterine infection could be responsible for the increased disease severity.