A 250‐kDa glycoprotein of <i>Naegleria fowleri</i> induces protection and modifies the expression of α4β1 and LFA‐1 on T and B lymphocytes in mouse meningitis model

Castillo-Ramírez, Diego A; Carrasco-Yépez, María Maricela; Rodríguez-Mera, Itzel Berenice; Reséndiz-Albor, Aldo Arturo; Rosales-Cruz, Érica; Rojas-Hernández, Saúl

doi:10.1111/pim.12882

Cited by 4 publications

(3 citation statements)

References 52 publications

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“…In addition, when mice were immunized with total extract of N. fowleri alone or coadministered with CT, an increment of the levels of IgG and IgA antibodies were detected in serum, nasal washes, and in the nasal cavity of mice. Furthermore, some important antigens of N. fowleri have been found highly immunogenic as the response of IgG and IgA is directed strongly towards some N. fowleri polypeptide bands (Carrasco-Yepez et al 2013;Castillo-Ramírez et al 2021;Cervantes-Sandoval et al 2010;Gutiérrez-Sánchez et al 2020).…”

Section: Discussionmentioning

confidence: 99%

Role of FcγRIII in the nasal cavity of BALB/c mice in the primary amebic meningoencephalitis protection model

et al. 2023

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Different mechanisms of the host immune response against the primary amebic meningoencephalitis (PAM) in the mouse protection model have been described. It has been proposed that antibodies opsonize Naegleria fowleri trophozoites; subsequently, the polymorphonuclear cells (PMNs) surround the trophozoites to avoid the infection. FcγRs activate signaling pathways of adapter proteins such as Syk and Hck on PMNs to promote different effector cell functions which are induced by the Fc portion of the antibody-antigen complexes. In this work, we analyzed the activation of PMNs, epithelial cells, and nasal passage cells via the expression of Syk and Hck genes. Our results showed an increment of the FcγRIII and IgG subclasses in the nasal cavity from immunized mice as well as Syk and Hck expression was increased, whereas in the in vitro assay, we observed that when the trophozoites of N. fowleri were opsonized with IgG anti-N. fowleri and interacted with PMN, the expression of Syk and Hck was also increased. We suggest that PMNs are activated via their FcγRIII, which leads to the elimination of the trophozoites in vitro, while in the nasal cavity, the adhesion and consequently infection are avoided.

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Section: Discussionmentioning

confidence: 99%

Role of FcγRIII in the nasal cavity of BALB/c mice in the primary amebic meningoencephalitis protection model

et al. 2023

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“…Here we describe some characteristics that have been attributed to this protein band. The 250-kDa band has been considered with mucinolytic activity and capable of degrading collagen (Chávez-Munguía et al 2014 ; Martínez-Castillo et al 2016 ); in addition, immunogenic properties have been attributed to this polypeptide band capable to provide 80% protection in mice immunized and challenged with lethal dose of N. fowleri trophozoites (Castillo-Ramírez et al 2021 ; Rojas-Hernández et al 2020 ). The fact that our antibody recognized different bands does not represent the lack of specificity of our antibody.…”

Section: Discussionmentioning

confidence: 99%

Role of cathepsin B of Naegleria fowleri during primary amebic meningoencephalitis

et al. 2022

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Naegleria fowleri causes primary amoebic meningoencephalitis in humans and experimental animals. It has been suggested that cysteine proteases of parasites play key roles in metabolism, nutrient uptake, host tissue invasion, and immune evasion. The aim of this work was to evaluate the presence, expression, and role of cathepsin B from N. fowleri in vitro and during PAM. Rabbit-specific polyclonal antibodies against cathepsin B were obtained from rabbit immunization with a synthetic peptide obtained by bioinformatic design. In addition, a probe was designed from mRNA for N. fowleri cathepsin B. Both protein and messenger were detected in fixed trophozoites, trophozoites interacted with polymorphonuclear and histological sections of infected mice. The main cathepsin B distribution was observed in cytoplasm or membrane mainly pseudopods and food-cups while messenger was in nucleus and cytoplasm. Surprisingly, both the messenger and enzyme were observed in extracellular medium. To determine cathepsin B release, we used trophozoites supernatant recovered from nasal passages or brain of infected mice. We observed the highest release in supernatant from recovered brain amoebae, and when we analyzed molecular weight of secreted proteins by immunoblot, we found 30 and 37 kDa bands which were highly immunogenic. Finally, role of cathepsin B during N. fowleri infection was determined; we preincubated trophozoites with E-64, pHMB or antibodies with which we obtained 60%, 100%, and 60% of survival, respectively, in infected mice. These results suggest that cathepsin B plays a role during pathogenesis caused by N. fowleri mainly in adhesion and contributes to nervous tissue damage.

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“…After conducting a series of in vitro studies, the most promising compounds against N. fowleri should be tested in vivo to proceed further with the lead development process. Several studies have reported animal models of the parasite [ 35 , 36 ], which can be considered by researchers working on anti-Naegleria drug discovery.…”

Section: Discussionmentioning

confidence: 99%

Imidazothiazole Derivatives Exhibited Potent Effects against Brain-Eating Amoebae

et al. 2022

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Naegleria fowleri (N. fowleri) is a free-living, unicellular, opportunistic protist responsible for the fatal central nervous system infection, primary amoebic meningoencephalitis (PAM). Given the increase in temperatures due to global warming and climate change, it is estimated that the cases of PAM are on the rise. However, there is a current lack of awareness and effective drugs, meaning there is an urgent need to develop new therapeutic drugs. In this study, the target compounds were synthesized and tested for their anti-amoebic properties against N. fowleri. Most compounds exhibited significant amoebicidal effects against N. fowleri; for example, 1h, 1j, and 1q reduced N. fowleri’s viability to 15.14%, 17.45% and 28.78%, respectively. Furthermore, the majority of the compounds showed reductions in amoeba-mediated host death. Of interest are the compounds 1f, 1k, and 1v, as they were capable of reducing the amoeba-mediated host cell death to 52.3%, 51%, and 56.9% from 100%, respectively. Additionally, these compounds exhibit amoebicidal properties as well; they were found to decrease N. fowleri’s viability to 26.41%, 27.39%, and 24.13% from 100%, respectively. Moreover, the MIC50 values for 1e, 1f, and 1h were determined to be 48.45 µM, 60.87 µM, and 50.96 µM, respectively. Additionally, the majority of compounds were found to exhibit limited cytotoxicity, except for 1l, 1o, 1p, 1m, 1c, 1b, 1zb, 1z, 1y, and 1x, which exhibited negligible toxicity. It is anticipated that these compounds may be developed further as effective treatments against these devastating infections due to brain-eating amoebae.

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A 250‐kDa glycoprotein of Naegleria fowleri induces protection and modifies the expression of α4β1 and LFA‐1 on T and B lymphocytes in mouse meningitis model

Cited by 4 publications

References 52 publications

Role of FcγRIII in the nasal cavity of BALB/c mice in the primary amebic meningoencephalitis protection model

Role of FcγRIII in the nasal cavity of BALB/c mice in the primary amebic meningoencephalitis protection model

Role of cathepsin B of Naegleria fowleri during primary amebic meningoencephalitis

Imidazothiazole Derivatives Exhibited Potent Effects against Brain-Eating Amoebae

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