Passive immunization with anti-ActA and anti-listeriolysin O antibodies protects against Listeria monocytogenes infection in mice

Asano, Kozo; Sashinami, Hiroshi; Osanai, Arihiro; Hirose, Shouhei; Ono, Hisaya K.; Narita, Kouji; Hu, Dong‐Liang; Nakane, Akio

doi:10.1038/srep39628

Cited by 6 publications

(6 citation statements)

References 33 publications

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“…Antibodies are considered irrelevant for protection against L. monocytogenes (Mackaness, 1962 ; Portnoy et al , 2002 ; Asano et al , 2016 ). However, a recent study could demonstrate that pregnancy causes altered glycosylation of IgG.…”

Section: Resultsmentioning

confidence: 99%

Pregnancy‐induced transfer of pathogen‐specific T cells from mother to fetus in mice

Yüzen,

Urbschat,

Schepanski

et al. 2023

EMBO Reports

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Neonatal health is determined by the transfer of maternal antibodies from the mother to the fetus. Besides antibodies, maternal cells cross the placental barrier and seed into fetal organs. Contrary to maternal antibodies, maternal microchimeric cells (MMc) show a high longevity, as they can persist in the offspring until adulthood. Recent evidence highlights that MMc leukocytes promote neonatal immunity against early‐life infections in mice and humans. As shown in mice, this promotion of immunity was attributable to an improved fetal immune development. Besides this indirect effect, MMc may be pathogen‐specific and thus, directly clear pathogen threats in the offspring postnatally. By using ovalbumin recombinant Listeria monocytogenes (LmOVA), we here provide evidence that OVA‐specific T cells are transferred from the mother to the fetus, which is associated with increased activation of T cells and a milder course of postnatal infection in the offspring. Our data highlight that maternally‐derived passive immunity of the neonate is not limited to antibodies, as MMc have the potential to transfer immune memory between generations.

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Section: Resultsmentioning

confidence: 99%

Pregnancy‐induced transfer of pathogen‐specific T cells from mother to fetus in mice

Yüzen,

Urbschat,

Schepanski

et al. 2023

EMBO Reports

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“…We therefore wanted to determine the localisation of replicative vs non-replicative bacteria, to determine if non-replicative bacteria were merely those that failed to escape the phagosome. We used phalloidin staining to detect actin ( Figure 1E ) and lysosomal-associated membrane protein 1 (LAMP1) staining ( Figure S1 ) to determine cytoplasmic or phagosomal location, respectively ( 31 – 36 ). We found that 81% (±5%) of replicative bacteria co-localised with actin and thus were present in the host cell cytoplasm ( Figure 1F ), while 17% (±1%) did not colocalise with actin so were predicted to be localised in phagosomes ( Figure 1G ).…”

Section: Resultsmentioning

confidence: 99%

Live-cell imaging reveals single-cell and population-level infection strategies of Listeria monocytogenes in macrophages

Moran,

Feltham,

Bagnall

et al. 2023

Front. Immunol.

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Pathogens have developed intricate strategies to overcome the host’s innate immune responses. In this paper we use live-cell microscopy with a single bacterium resolution to follow in real time interactions between the food-borne pathogen L. monocytogenes and host macrophages, a key event controlling the infection in vivo. We demonstrate that infection results in heterogeneous outcomes, with only a subset of bacteria able to establish a replicative invasion of macrophages. The fate of individual bacteria in the same host cell was independent from the host cell and non-cooperative, being independent from co-infecting bacteria. A higher multiplicity of infection resulted in a reduced probability of replication of the overall bacterial population. By use of internalisation assays and conditional probabilities to mathematically describe the two-stage invasion process, we demonstrate that the higher MOI compromises the ability of macrophages to phagocytose bacteria. We found that the rate of phagocytosis is mediated via the secreted Listeriolysin toxin (LLO), while the probability of replication of intracellular bacteria remained constant. Using strains expressing fluorescent reporters to follow transcription of either the LLO-encoding hly or actA genes, we show that replicative bacteria exhibited higher PrfA regulon expression in comparison to those bacteria that did not replicate, however elevated PrfA expression per se was not sufficient to increase the probability of replication. Overall, this demonstrates a new role for the population-level, but not single cell, PrfA-mediated activity to regulate outcomes of host pathogen interactions.

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“…In this aspect, antibodies may offer an interesting alternative to antibiotics in the near future. Indeed, mAbs against Ferritin-like protein (Flp), ActA, or Listeriolysin O (LLO) have shown promising results in protecting mice against Listeria infection ( 50 , 51 ). Thus, the recombinant human mAbs presented here could be an interesting alternative for passive immunization to reduce the number of deaths caused by listeriosis.…”

Section: Resultsmentioning

confidence: 99%

Phage Display-Derived Monoclonal Antibodies Against Internalins A and B Allow Specific Detection of Listeria monocytogenes

Moreira

Gronow

Dübel

et al. 2022

Front. Public Health

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Listeria monocytogenes is the causative agent of listeriosis, a highly lethal disease initiated after the ingestion of Listeria-contaminated food. This species comprises different serovars, from which 4b, 1/2a, and 1/2b cause most of the infections. Among the different proteins involved in pathogenesis, the internalins A (InlA) and B (InlB) are the best characterized, since they play a major role in the enterocyte entry of Listeria cells during early infection. Due to their covalent attachment to the cell wall and location on the bacterial surface, along with their exclusive presence in the pathogenic L. monocytogenes, these proteins are also used as detection targets for this species. Even though huge advancements were achieved in the enrichment steps for subsequent Listeria detection, few studies have focused on the improvement of the antibodies for immunodetection. In the present study, recombinant InlA and InlB produced in Escherichia coli were used as targets to generate antibodies via phage display using the human naïve antibody libraries HAL9 and HAL10. A set of five recombinant antibodies (four against InlA, and one against InlB) were produced in scFv-Fc format and tested in indirect ELISA against a panel of 19 Listeria strains (17 species; including the three main serovars of L. monocytogenes) and 16 non-Listeria species. All five antibodies were able to recognize L. monocytogenes with 100% sensitivity (CI 29.24–100.0) and specificity (CI 88.78–100.0) in all three analyzed antibody concentrations. These findings show that phage display-derived antibodies can improve the biological tools to develop better immunodiagnostics for L. monocytogenes.

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Passive immunization with anti-ActA and anti-listeriolysin O antibodies protects against Listeria monocytogenes infection in mice

Cited by 6 publications

References 33 publications

Pregnancy‐induced transfer of pathogen‐specific T cells from mother to fetus in mice

Pregnancy‐induced transfer of pathogen‐specific T cells from mother to fetus in mice

Live-cell imaging reveals single-cell and population-level infection strategies of Listeria monocytogenes in macrophages

Phage Display-Derived Monoclonal Antibodies Against Internalins A and B Allow Specific Detection of Listeria monocytogenes

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