Intracellular<i>Haemophilus influenzae</i>invades the brain

Parisi, Dana N; Martinez, Luis R.

doi:10.4161/viru.36086

Cited by 5 publications

(3 citation statements)

References 16 publications

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“…The two tested species in this study , N. flavescens and H. parainfluenzae , were found to induce cytotoxicity by intracellular infection. While the genera Neisseria and Haemophilus are known to be capable of causing intracellular infection as exemplified by Haemophilus influenzae and Neisseria meningiditis (Nikulin et al, 2006 ; Parisi and Martinez, 2014 ), this is the first report of internalization of N. flavescens and H. parainfluenzae per se . Interestingly, H. parainfluenzae showed significantly less cytotoxicity against non-cancer TIGK cells as compared to OSCC cells.…”

Section: Discussionmentioning

confidence: 73%

Screening of Health-Associated Oral Bacteria for Anticancer Properties in vitro

Baraniya

Jain

Lucarelli

et al. 2020

Front. Cell. Infect. Microbiol.

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While extensive literature exists about the role of oral bacterial pathogens like Porphyromonas gingivalis and Fusobacterium nucleatum in oral squamous cell carcinoma (OSCC), the role of health-associated species has been largely unexplored. In this study, we assessed the effect of Streptococcus mitis, Rothia mucilaginosa, Neisseria flavescens, Haemophilus parainfluenzae, Lautropia mirabilis , and Veillonella parvula on proliferation and expression of marker genes (IL-6, TNF-α, MMP3, CD36, CCD1, and NANOG) in OSCC cell lines CAL27, SCC25, and SCC4. Porphyromonas gingivalis was included as a pathogenic control. Both bacterial lysates (3 concentrations) and live cells (3 MOIs) were tested. S. mitis, H. parainfluenzae , and N. flavescens resulted in substantial, dose-dependent reduction of proliferation, which was found to be mediated by H 2 O 2 for the former and intracellular infection in the latter two species. However, only H. parainfluenzae showed differential antiproliferative effect against the cancer cell lines vs. the normal control (TIGKs). In the gene expression assays, the health-associated species mostly downregulated CD36, a gene that plays an important role in tumor growth and metastasis, while P. gingivalis upregulated it. IL6 and TNF expression, on the other hand, was upregulated by almost all species, particularly the Gram-negatives including P. gingivalis . The effect on other genes was less evident and varied significantly by cell line. This exploratory study is the first insight into how health-associated bacteria may interact with OSCC. Further studies to explore whether the observed effects may have implications for the prevention or treatment of oral cancer are warranted.

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Section: Discussionmentioning

confidence: 73%

Screening of Health-Associated Oral Bacteria for Anticancer Properties in vitro

Baraniya

Jain

Lucarelli

et al. 2020

Front. Cell. Infect. Microbiol.

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“…A critical step during meningitis pathogenesis is the bacterial crossing of brain barriers (BBB or BCSFB) and their entry into the CNS. Several studies investigated the impact of the BBB during Haemophilus meningitis [ 72 , 73 , 74 , 75 , 76 , 77 ]. However, early studies with rhesus monkeys indicate that Haemophilus enters the brain via the BSCFB [ 40 , 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Non-Typeable Haemophilus influenzae Invade Choroid Plexus Epithelial Cells in a Polar Fashion

Wegele

Stump-Guthier

Moroniak

et al. 2020

IJMS

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Non-typeable Haemophilus influenzae (NTHI) is a pathogen of the human respiratory tract causing the majority of invasive H. influenzae infections. Severe invasive infections such as septicemia and meningitis occur rarely, but the lack of a protecting vaccine and the increasing antibiotic resistance of NTHI impede treatment and emphasize its relevance as a potential meningitis causing pathogen. Meningitis results from pathogens crossing blood–brain barriers and invading the immune privileged central nervous system (CNS). In this study, we addressed the potential of NTHI to enter the brain by invading cells of the choroid plexus (CP) prior to meningeal inflammation to enlighten NTHI pathophysiological mechanisms. A cell culture model of human CP epithelial cells, which form the blood–cerebrospinal fluid barrier (BCSFB) in vivo, was used to analyze adhesion and invasion by immunofluorescence and electron microscopy. NTHI invade CP cells in vitro in a polar fashion from the blood-facing side. Furthermore, NTHI invasion rates are increased compared to encapsulated HiB and HiF strains. Fimbriae occurrence attenuated adhesion and invasion. Thus, our findings underline the role of the BCSFB as a potential entry port for NTHI into the brain and provide strong evidence for a function of the CP during NTHI invasion into the CNS during the course of meningitis.

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“…Later studies showed that the permeability of the BBB was also increased in rats after inoculation with H. influenzae outer membrane vesicles (OMV), suggesting a role for these vesicles in transporting Hib LPS to the CSF during meningitis [191]. Furthermore, it was shown that zyxin, a cytoskeletal protein implicated in the protection of TJs in the BBB, is critical for the integrity of the BBB and, as a consequence, for protecting against invading pathogens such as H. influenzae [192]. Overall, the inflammatory response of patients during the infection with H. influenzae is determined by several virulence factors including the capsule, adhesion proteins, pili and outer membrane proteins as well as LPS and IgA1 protease [193].…”

Section: Roles Of Bacterial Virulence Factors During Invasion Thromentioning

confidence: 99%

Virulence Factors of Meningitis-Causing Bacteria: Enabling Brain Entry across the Blood–Brain Barrier

Herold

Schroten

Schwerk

2019

IJMS

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Infections of the central nervous system (CNS) are still a major cause of morbidity and mortality worldwide. Traversal of the barriers protecting the brain by pathogens is a prerequisite for the development of meningitis. Bacteria have developed a variety of different strategies to cross these barriers and reach the CNS. To this end, they use a variety of different virulence factors that enable them to attach to and traverse these barriers. These virulence factors mediate adhesion to and invasion into host cells, intracellular survival, induction of host cell signaling and inflammatory response, and affect barrier function. While some of these mechanisms differ, others are shared by multiple pathogens. Further understanding of these processes, with special emphasis on the difference between the blood–brain barrier and the blood–cerebrospinal fluid barrier, as well as virulence factors used by the pathogens, is still needed.

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IntracellularHaemophilus influenzaeinvades the brain

Cited by 5 publications

References 16 publications

Screening of Health-Associated Oral Bacteria for Anticancer Properties in vitro

Screening of Health-Associated Oral Bacteria for Anticancer Properties in vitro

Non-Typeable Haemophilus influenzae Invade Choroid Plexus Epithelial Cells in a Polar Fashion

Virulence Factors of Meningitis-Causing Bacteria: Enabling Brain Entry across the Blood–Brain Barrier

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