A Light Microscopy Study of the Migration of Naegleria fowleri from the Nasal Submucosa to the Central Nervous System during the Early Stage of Primary Amebic Meningoencephalitis in Mice

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

doi:10.2307/3284907

Cited by 37 publications

(55 citation statements)

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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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“…Mice were separated into groups of 3 and killed at time periods of 24,32,48,72,96, and 120 hours postinoculation. No mice died before the end of the time periods studied (Jarolim et al 2000).…”

Section: Methodsmentioning

confidence: 99%

“…A condition similar to human PAM can be experimentally produced in mice when inoculated intranasally with N. fowleri (Duma 1972, Martinez et al 1973b). The primary pathway taken by N. fowleri from the nasal mucosa to the central nervous system (CNS) during the initial stages of PAM has been elucidated (Jarolim et al 2000). The possible involvement of the blood vessels and lungs in early stage dissemination of this rapidly fatal disease remains a question.…”

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confidence: 99%

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

Jarolim¹,

McCosh²,

Howard³

2002

FOLIA PARASIT

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Abstract. Primary amoebic meningoencephalitis (PAM) was induced in mice by intranasal inoculation of Naegleria fowleri (Singh et Das, 1970) to study the role of the blood vessels and lungs in the early and later stages in this disease. Upon culturing blood and lung tissue obtained at 24-, 36-, 48-, 72-, 96-, and 120-hour time periods, it was found that amoebae grew only from blood and lung tissue obtained at the 96 and 120 hour time periods. Paraffin sections of the head revealed small foci of acute inflammation and amoebae within the olfactory bulb of the central nervous system (CNS) at 24 hours. Amoebae were not observed within blood vessels of the CNS until 96 and 120 hours. Also, amoebae were observed within the connective tissue surrounding blood vessels and sutures of the skull, bone marrow, and venous sinusoids between the skull bone tables at 96 and 120 hours. No amoebae or acute inflammatory reactions were observed in the lung sections from any time period and indirect immunofluorescence microscopy was negative for N. fowleri. This study provides evidence that neither blood vessels nor lungs provide routes for N. fowleri to the CNS during the early stages of PAM and that amoebae enter veins of the CNS and bone marrow during later stages of the disease.

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“…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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A Light Microscopy Study of the Migration of Naegleria fowleri from the Nasal Submucosa to the Central Nervous System during the Early Stage of Primary Amebic Meningoencephalitis in Mice

Cited by 37 publications

References 0 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

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

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

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