The role of blood vessels and lungs in the dissemination of Naegleria fowleri following intranasal inoculation in mice

Jarolim, Kirby L.; McCosh, Jeffrey K.; Howard, Marsha J.

doi:10.14411/fp.2002.035

Cited by 16 publications

(13 citation statements)

References 6 publications

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“…These results confirmed previous experiments with BSM and PSM, and showed that the mucin MUC5AC may be an important protective barrier, reducing adhesion and cytotoxicity to the airway epithelium. Histopathological studies using a murine model have shown that this amoeba infects its host by invading the olfactory mucosa, migrating through the olfactory nerves, crossing the cribiform plate, and entering the olfactory bulbs (Carter, 1970;Jarolim et al, 2000Jarolim et al, , 2002. At the very early stages of infection, trophozoites are observed at the lumen of the nasal cavity embedded in mucus secretions (Rojas-Hernández et al, 2004).…”

Section: Nci-h292 Cells and Muc5ac Assaysmentioning

confidence: 99%

“…It has been demonstrated that this protozoan gains access to the CNS by penetrating the olfactory neuroepithelium and invading the olfactory bulbs (Carter, 1970;Jarolim et al, 2000Jarolim et al, , 2002Rojas-Hernández et al, 2004). Once in the CNS, the amoebae induce a strong inflammatory response with lysis of leukocytes that contributes to tissue damage (Cervantes-Sandoval et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Mucins in the host defence against Naegleria fowleri and mucinolytic activity as a possible means of evasion

et al. 2008

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Naegleria fowleri is the aetiological agent of primary amoebic meningoencephalitis (PAM). This parasite invades its host by penetrating the olfactory mucosa. During the initial stages of infection, the host response is initiated by the secretion of mucus that traps the trophozoites. Despite this response, some trophozoites are able to reach, adhere to and penetrate the epithelium. In the present work, we evaluated the effect of mucins on amoebic adherence and cytotoxicity to Madin-Darby canine kidney (MDCK) cells and the MUC5AC-inducing cell line NCI-H292. We showed that mucins inhibited the adhesion of amoebae to both cell lines; however, this inhibition was overcome in a time-dependent manner. N. fowleri re-established the capacity to adhere faster than N. gruberi. Moreover, mucins reduced the cytotoxicity to target cells and the progression of the illness in mice. In addition, we demonstrated mucinolytic activity in both Naegleria strains and identified a 37 kDa protein with mucinolytic activity. The activity of this protein was inhibited by cysteine protease inhibitors. Based on these results, we suggest that mucus, including its major mucin component, may act as an effective protective barrier that prevents most cases of PAM; however, when the number of amoebae is sufficient to overwhelm the innate immune response, the parasites may evade the mucus by degrading mucins via a proteolytic mechanism.

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Section: Nci-h292 Cells and Muc5ac Assaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mucins in the host defence against Naegleria fowleri and mucinolytic activity as a possible means of evasion

et al. 2008

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“…fowleri is the causal agent of PAM, and the acquisition of this entity is commonly associated with a recent history of aquatic activity by the patient (Schuster & Visvesvara, 2004). The route of invasion of N. fowleri has been analysed by histopathological studies using a mouse model (Carter, 1970;Cervantes-Sandoval et al, 2008a;Jaroli et al, 2002). These studies revealed that the amoeba infects the host by first penetrating the olfactory mucosa and subsequently crossing the cribriform plate of the ethmoid bone, eventually reaching the olfactory bulbs of the CNS.…”

Section: Discussionmentioning

confidence: 99%

“…PAM is an acute and rapidly fatal infection that is characterized by parasitic invasion of the central nervous system (CNS). The parasite gains access to the CNS by penetrating the olfactory neuroepithelium and migrating through olfactory nerves until it reaches the olfactory bulbs (Carter, 1970;Jaroli et al, 2002;Jarolim et al, 2000;Rojas-Hernández et al, 2004;Shibayama et al, 2003). Immunohistochemical studies of the early events of infection using a murine model have shown that the amoebae induce intense mucus secretion and an inflammatory reaction in the nasal cavity (Cervantes-Sandoval et al, 2008a;Rojas-Hernández et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Disruption of MDCK cell tight junctions by the free-living amoeba Naegleria fowleri

et al. 2013

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Naegleria fowleri is the aetiological agent of primary amoebic meningoencephalitis. This parasite invades its host by penetrating the olfactory mucosa. However, the mechanism of epithelium penetration is not well understood. In the present study, we evaluated the effect of N. fowleri trophozoites and the non-pathogenic Naegleria gruberi on Madin-Darby canine kidney (MDCK) tight junction proteins, including claudin-1, occludin and ZO-1, as well as on the actin cytoskeleton. Trophozoites from each of the free-living amoeba species were co-cultured with MDCK cells in a 1 : 1 ratio for 1, 3, 6 or 10 h. Light microscopy revealed that N. fowleri caused morphological changes as early as 3 h post-infection in an epithelial MDCK monolayer. Confocal microscopy analysis revealed that after 10 h of co-culture, N. fowleri trophozoites induced epithelial cell damage, which was characterized by changes in the actin apical ring and disruption of the ZO-1 and claudin-1 proteins but not occludin. Western blot assays revealed gradual degradation of ZO-1 and claudin-1 as early as 3 h post-infection. Likewise, there was a drop in transepithelial electrical resistance that resulted in increased epithelial permeability and facilitated the invasion of N. fowleri trophozoites by a paracellular route. In contrast, N. gruberi did not induce alterations in MDCK cells even at 10 h post-infection. Based on these results, we suggest that N. fowleri trophozoites disrupt epithelial monolayers, which could enable their penetration of the olfactory epithelium and subsequent invasion of the central nervous system.

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“…The infection usually occurs after performing aquatic activities in water bodies containing the parasite (Schuster & Visvesvara, 2004;Marciano-Cabral & Cabral, 2007). Histopathological studies using a mouse model showed that the amoebae infect the host by penetrating the olfactory mucosa, migrating through the olfactory nerves, and passing through the cribriform plate to reach the olfactory bulbs of the CNS, where an intense inflammatory reaction is produced (Carter, 1970;Jarolim et al, 2000Jarolim et al, , 2002Cervantes-Sandoval et al, 2008a). In the very early stages of infection, trophozoites are seen in the lumen of the nasal cavity embedded in a large amount of mucus and surrounded by infiltrated neutrophils (Thong et al, 1983;Rojas-Hernández et al, 2004;Cervantes-Sandoval et al, 2008b).…”

Section: Discussionmentioning

confidence: 99%

Naegleria fowleri induces MUC5AC and pro-inflammatory cytokines in human epithelial cells via ROS production and EGFR activation

et al. 2009

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Naegleria fowleri is an amoeboflagellate responsible for the fatal central nervous system (CNS) disease primary amoebic meningoencephalitis (PAM). This amoeba gains access to the CNS by invading the olfactory mucosa and crossing the cribriform plate. Studies using a mouse model of infection have shown that the host secretes mucus during the very early stages of infection, and this event is followed by an infiltration of neutrophils into the nasal cavity. In this study, we investigated the role of N. fowleri trophozoites in inducing the expression and secretion of airway mucin and pro-inflammatory mediators. Using the human mucoepidermal cell line NCI-H292, we demonstrated that N. fowleri induced the expression of the MUC5AC gene and protein and the pro-inflammatory mediators interleukin-8 (IL-8) and interleukin-1b (IL-1b), but not tumour necrosis factor-a or chemokine c-c motif ligand 11 (eotaxin). Since the production of reactive oxygen species (ROS) is a common phenomenon involved in the signalling pathways of these molecules, we analysed if trophozoites were capable of causing ROS production in NCI-H292 cells by detecting oxidation of the fluorescent probe 2,7-dichlorofluorescein diacetate. NCI-H292 cells generated ROS after 15-30 min of trophozoite stimulation. Furthermore, the expression of MUC5AC, IL-8 and IL-1b was inhibited in the presence of the ROS scavenger DMSO. In addition, the use of an epidermal growth factor receptor inhibitor decreased the expression of MUC5AC and IL-8, but not IL-1b. We conclude that N. fowleri induces the expression of some host innate defence mechanisms, such as mucin secretion (MUC5AC) and local inflammation (IL-8 and IL-1b) in respiratory epithelial cells via ROS production and suggest that these innate immune mechanisms probably prevent most PAM infections.

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The role of blood vessels and lungs in the dissemination of Naegleria fowleri following intranasal inoculation in mice

Cited by 16 publications

References 6 publications

Mucins in the host defence against Naegleria fowleri and mucinolytic activity as a possible means of evasion

Mucins in the host defence against Naegleria fowleri and mucinolytic activity as a possible means of evasion

Disruption of MDCK cell tight junctions by the free-living amoeba Naegleria fowleri

Naegleria fowleri induces MUC5AC and pro-inflammatory cytokines in human epithelial cells via ROS production and EGFR activation

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