Maternal sepsis caused by Listeria monocytogenes with a fatal fetal outcome.

Improving maternal and child health is a global priority. Although infection with Listeria monocytogenes (LM), a small facultative anaerobic, gram-positive motile bacillus is rare, when it infects the maternal-fetoplacental unit, it can result in adverse fetal sequelae such as chorioamnionitis, preterm labour, neonatal sepsis, meningitis and neonatal death. Pregnancy-associated listeriosis may present with a plethora of diverse, non-specific symptoms such as fever, influenza-like or gastrointestinal symptoms, premature contractions and preterm labour. It has a predilection for the second and third trimester of pregnancy, occurring sporadically or as part of an outbreak, most of which have involved unpasteurised dairy products, long shelf life products, contaminated ready-to-eat food, deli meats and soft cheeses. Strains belonging to the clonal complexes 1, 4 and 6 are hypervigilant and are commonly associated with maternal-neonatal infections. Maternal listeriosis occurs as a direct consequence of LM-specific placental tropism, which is mediated by the conjugated action of internalin A and internalin B at the placental barrier. The diagnosis is established from placental culture. Penicillin, ampicillin and amoxicillin are the antimicrobials of choice. It has a high fetal morbidity of up to 30%. The authors present the case of a multiparous woman in her early 20s presenting with sepsis and preterm premature rupture of her membranes at 21 weeks gestation. A live baby was delivered spontaneously and died shortly after birth. Placental cultures and postmortem examination were consistent with the diagnosis of disseminated Listeria infection. Due to the increased susceptibility of pregnant women for LM, a high index of clinical suspicion is required to establish the diagnosis and initiate appropriate antimicrobial therapy to reduce adverse fetal outcomes.

Genomic characteristics of listeria that caused invasive listeriosis during the COVID-19 pandemic (preprint)

Invasive listeriosis is relatively rare, but is one of the deadliest food-borne infections, affecting pregnant women, their fetuses and newborn infants, the elderly and immunocompromised people. The aim of this study was to research the impact of the COVID-19 pandemic on invasive listeriosis in the metropolis. Loci and whole-genome sequencing with subsequent bioinformatic analysis were used for the study of clinical and food Listeria monocytogenes isolates revealed in 2018–2022. The results indicate the crucial change in the spectrum of the L. monocytogenes sequence types (ST) causing invasive listeriosis during the COVID-19 pandemic, with slight changes in the ST spectrum of the food isolates. An increase in sensitivity to previously non-human L. monocytogenes genotypes, namely ST8, 20, 21, 37, 391, and 425, was observed. L. monocytogenes of ST20 and 425 carried plasmids with virulence factors (VF), in addition to the 42 VF identified in the genomes with the vip gene exclusion in the genomes of ST7, 8, 21, and 37. Perinatal listeriosis cases were associated with the new hypervirulent L. monocytogenes of ST1, 4, and 219 compiled with old ST6. These data indicate the need for the more stringent control of food products for high-risk groups.

Hyper-Virulent Listeria monocytogenes Strains Associated With Respiratory Infections in Central Italy.

Listeria monocytogenes (Lm) is a foodborne pathogen causing listeriosis. Invasive forms of the disease mainly manifest as septicaemia, meningitis and maternal-neonatal infections. Lm-associated respiratory infections are very rare and little known. We reported two Lm respiratory infection cases occurred in Central Italy during the summer of 2020, in the midst of the SARS-CoV2 pandemic. In addition to collect the epidemiological and clinical characteristics of the patients, we used Whole Genome Sequencing to study the genomes of the Lm isolates investigating their virulence and antimicrobial profiles and the presence of genetic mobile elements. Both the strains belonged to hypervirulent MLST clonal complexes (CC). In addition to the Listeria Pathogenicity Island 1 (LIPI-1), the CC1 strain also carried LIPI-3 and the CC4 both LIPI-3 and LIPI-4. Genetic determinants for antimicrobial and disinfectants resistance were found. The CC1 genome presented prophage sequences but they did not interrupt the comK gene, involved in the phagosomal escape of Lm. None of the strains carried plasmids. Lm is an important, although rare, opportunistic pathogen for respiratory tract and lung infections. To avoid dangerous diagnostic delays of these severe clinical forms, it is important to sensitize hospital laboratories to this rare manifestation of listeriosis considering Lm in the differential diagnosis of respiratory infections.

Pulmonary insults exacerbate susceptibility to oral Listeria monocytogenes infection through the production of IL-10 by NK cells.

Most individuals who consume foods contaminated with the bacterial pathogen Listeria monocytogenes (Lm) develop mild symptoms, while others are susceptible to life-threatening systemic infections (listeriosis). Although it is known that the risk of severe disease is increased in certain human populations, including the elderly, it remains unclear why others who consume contaminated food develop listeriosis. Here, we used a murine model to discover that pulmonary coinfections can impair the host's ability to adequately control and eradicate systemic Lm that cross from the intestines to the bloodstream. We found that the resistance of mice to oral Lm infection was dramatically reduced by coinfection with Streptococcus pneumoniae (Spn), a bacterium that colonizes the respiratory tract and can also cause severe infections in the elderly. Exposure to Spn or microbial products, including a recombinant Lm protein (L1S) and lipopolysaccharide (LPS), rendered otherwise resistant hosts susceptible to severe systemic Lm infection. In addition, we show that this increase in susceptibility was dependent on an increase in the production of interleukin-10 (IL-10) from Ncr1+ cells, including natural killer (NK) cells. Lastly, the ability of Ncr1+ cell derived IL-10 to increase disease susceptibility correlated with a dampening of both myeloid cell accumulation and myeloid cell phagocytic capacity in infected tissues. These data suggest that efforts to minimize inflammation in response to an insult at the respiratory mucosa render the host more susceptible to infections by Lm and possibly other pathogens that access the oral mucosa.

Listeria Toxin Promotes Phosphorylation of the Inflammasome Adaptor ASC Through Lyn and Syk to Exacerbate Pathogen Expansion (preprint)

Inflammasome activation exacerbates infectious disease caused by pathogens such as Listeria monocytogenes, Staphylococcus aureus, and severe acute respiratory syndrome coronavirus 2. Although these pathogens activate host inflammasomes to regulate pathogen expansion, the mechanisms by which pathogen toxins contribute to inflammasome activation remain poorly understood. Here we show that activation of inflammasomes by Listeria infection was promoted by amino acid residue T223 of listeriolysin O (LLO) independently of its pore-forming activity. LLO T223 was critical for phosphorylation of the inflammasome adaptor ASC at amino acid residue Y144 through Lyn-Syk signaling, which was essential for ASC oligomerization. Notably, a Listeria mutant expressing LLO T223A was impaired in inducing ASC phosphorylation and inflammasome activation. Furthermore, the virulence of LLO T223A mutant was markedly attenuated in vivo due to impaired ability to activate the inflammasome. Our results reveal a previously unrecognized function of a pathogen toxin that exacerbates infection by promoting phosphorylation of ASC.

CD71+ Erythroid Cells in Human Neonates Exhibit Immunosuppressive Properties and Compromise Immune Response Against Systemic Infection in Neonatal Mice.

Newborns are highly susceptible to infectious diseases. The underlying mechanism of neonatal infection susceptibility has generally been related to their under-developed immune system. Nevertheless, this notion has recently been challenged by the discovery of the physiological abundance of immunosuppressive erythroid precursors CD71+erythroid cells (CECs) in newborn mice and human cord blood. Here, as proof of concept, we show that these cells are also abundant in the peripheral blood of human newborns. Although their frequency appears to be more variable compared to their counterparts in mice, they rapidly decline by 4 weeks of age. However, their proportion remains significantly higher in infants up to six months of age compared to older infants. We found CD45 expressing CECs, as erythroid progenitors, were the prominent source of reactive oxygen species (ROS) production in both humans and mice. Interestingly, a higher proportion of CD45+CECs was observed in the spleen versus bone marrow of neonatal mice, which was associated with a higher ROS production by splenic CECs compared to their siblings in the bone marrow. CECs from human newborns suppressed cytokine production by CD14 monocytes and T cells, which was partially abrogated by apocynin in vitro. Moreover, the depletion of CECs in neonatal mice increased the number of activated effector immune cells in their spleen and liver, which rendered them more resistant to Listeria monocytogenes infection. This was evident by a significant reduction in the bacteria load in the spleen, liver and brain of treated-mice compared to the control group, which enhanced their survival rate. Our finding highlights the immunoregulatory processes mediated by CECs in newborns. Thus, such tightly regulated immune system in newborns/infants may explain one potential mechanism for the asymptomatic or mild COVID-19 infection in this population.