Involvement of the capsular GalXM-induced IL-17 cytokine in the control of Cryptococcus neoformans infection

LaRocque-de-Freitas, Isabel Ferreira; Rocha, Juliana Dutra B.; Nunes, Marise P.; Oliveira, Priscila A V; Nascimento, Danielle de Oliveira; Freire-de-Lima, Leonardo; Takiya, Christina Maeda; Morrot, Alexandre; Decotè-Ricardo, Débora; Previato, José O.; DosReis, George A.; Mendonça-Previato, Lúcia; Freire-de-Lima, Célio Geraldo

doi:10.1038/s41598-018-34649-4

Cited by 19 publications

(22 citation statements)

References 113 publications

(117 reference statements)

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“…In order to fully understand the effect of K. pneumoniae LPS O2afg-antigen in modulating immune responses through NF-κB, these factors must also be considered and future studies will unravel their role in this immune evasion mechanism. When monocytes’ stimulation is performed with the LPS O2afg-antigen (either from 6613 or ST258), PMB seems to restore the levels of pro-inflammatory molecules ( Figure 3 B,C,E), which suggests that PMB could not only act as a negative immune-modulator of inflammatory response, but, at an early stage, it could revert immune evasion as previously demonstrated for other bacterial LPS [ 47 , 48 , 49 , 50 ].…”

Section: Discussionsupporting

confidence: 72%

Klebsiella pneumoniae Lipopolysaccharides Serotype O2afg Induce Poor Inflammatory Immune Responses Ex Vivo

et al. 2021

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Currently, Klebsiella pneumoniae is a pathogen of clinical relevance due to its plastic ability of acquiring resistance genes to multiple antibiotics. During K. pneumoniae infections, lipopolysaccharides (LPS) play an ambiguous role as they both activate immune responses but can also play a role in immune evasion. The LPS O2a and LPS O2afg serotypes are prevalent in most multidrug resistant K. pneumoniae strains. Thus, we sought to understand if those two particular LPS serotypes were involved in a mechanism of immune evasion. We have extracted LPS (serotypes O1, O2a and O2afg) from K. pneumoniae strains and, using human monocytes ex vivo, we assessed the ability of those LPS antigens to induce the production of pro-inflammatory cytokines and chemokines. We observed that, when human monocytes are incubated with LPS serotypes O1, O2a or O2afg strains, O2afg and, to a lesser extent, O2a but not O1 failed to elicit the production of pro-inflammatory cytokines and chemokines, which suggests a role in immune evasion. Our preliminary data also shows that nuclear translocation of NF-κB, a process which regulates an immune response against infections, occurs in monocytes incubated with LPS O1 and, to a smaller extent, with LPS O2a, but not with the LPS serotype O2afg. Our results indicate that multidrug resistant K. pneumoniae expressing LPS O2afg serotypes avoid an initial inflammatory immune response and, consequently, are able to systematically spread inside the host unharmed, which results in the several pathologies associated with this bacterium.

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Section: Discussionsupporting

confidence: 72%

Klebsiella pneumoniae Lipopolysaccharides Serotype O2afg Induce Poor Inflammatory Immune Responses Ex Vivo

et al. 2021

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“…Similar to IFN-γ, IL-17 appears to play an important role in controlling infection by Cryptococcus spp. In a model of infection by C. neoformans (B3501 strain) in C57BL/6 IL-17-deficient mice, the role of this cytokine in controlling the disease was identified 35 , mainly due to the activity modulator of GXM. It has also been described www.nature.com/scientificreports/ that, in a model of infection by C. neoformans, a greater infiltration of Th17 lymphocytes was observed in the lungs of C57BL/6 mice, as well as an increased amount of IL-17 in this tissue 57 .…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have described the importance of the Th17 response in the control of fungal infections, especially in opportunistic fungal models such as C. neoformans, C. albicans and A. fumigatus 35,37,50,51 . IL-17A is important for total lung leukocyte recruitment and accumulation 14 days after infection by C. neoformans, as well as the reduction of inflammation and increase in fungal load 50 .…”

Section: Tlr9 −/− Mice Have Higher Fungal Load In the Brain And Spleementioning

confidence: 99%

“…The stimulation triggers intracellular signaling dependent on recruitment and interaction with MyD88, leading to the activation of macrophages, dendritic cells (DCs) and B cells, and the production of cytokines, chemokines, and immunoglobulins 34 . Subsequently, cytokines produced by DCs, such as IL-12 or IL-6, induce the differentiation of naive T cells into Th1 and Th17 35 , respectively. Studies using murine models have demonstrated that the control of spread and infection by Cryptococcus requires a cellular and molecular adaptive response, involving the Th1 and Th17-type immune response [36][37][38][39] .…”

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confidence: 99%

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The role of Toll-like receptor 9 in a murine model of Cryptococcus gattii infection

Silva-Junior

Firmino-Cruz

Guimarães-de-Oliveira

et al. 2021

Sci Rep

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Toll-like receptor 9 (TLR9) is crucial to the host immune response against fungi, such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, but its importance in Cryptococcus gattii infection is unknown. Our study aimed to understand the role of TLR9 during the course of experimental C. gattii infection in vivo, considering that the cryptococcal DNA interaction with the receptor could contribute to host immunity even in an extremely susceptible model. We inoculated C57BL/6 (WT) and TLR9 knock-out (TLR9−/−) mice intratracheally with 104C. gattii yeast cells. TLR9−/− mice had a higher mortality rate compared to WT mice and more yeast cells that had abnormal size, known as titan cells, in the lungs. TLR9−/− mice also had a greater number of CFUs in the spleen and brain than WT mice, in addition to having lower levels of IFN-γ and IL-17 in the lung. With these markers of aggressive cryptococcosis, we can state that TLR9−/− mice are more susceptible to C. gattii, probably due to a mechanism associated with the decrease of a Th1 and Th17-type immune response that promotes the formation of titan cells in the lungs. Therefore, our results indicate the participation of TLR9 in murine resistance to C. gattii infection.

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“…Recently, it was demonstrated that treatment with GalXM activates dendritic cells and induces Th17 differentiation when co-cultured with T cells. The authors also demonstrated that treating mice with GalXM prior to infection induced immune protection and this phenomenon was dependent on IL-6 and IL-17 production (108).…”

Section: Immunomodulatory Activity Of Galxmmentioning

confidence: 99%

Immunomodulatory Role of Capsular Polysaccharides Constituents of Cryptococcus neoformans

et al. 2019

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Cryptococcosis is a systemic fungal infection caused by Cryptococcus neoformans . In immunocompetent patients, cryptococcal infection is often confined to the lungs. In immunocompromised individuals, C. neoformans may cause life-threatening illness, either from novel exposure or through reactivation of a previously acquired latent infection. For example, cryptococcal meningitis is a severe clinical disease that can manifest in people that are immunocompromised due to AIDS. The major constituents of the Cryptococcus polysaccharide capsule, glucuronoxylomannan (GXM), and galactoxylomannan (GalXM), also known as glucuronoxylomanogalactan (GXMGal), are considered the primary virulence factors of Cryptococcus . Despite the predominance of GXM in the polysaccharide capsule, GalXM has more robust immunomodulatory effects on host cellular immunity. This review summarizes current knowledge regarding host- Crytococcus neoformans interactions and the role of capsular polysaccharides in host immunomodulation. Future studies will likely facilitate a better understanding of the mechanisms involved in antigenic recognition and host immune response to C. neoformans and lead to the development of new therapeutic pathways for cryptococcal infection.

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Involvement of the capsular GalXM-induced IL-17 cytokine in the control of Cryptococcus neoformans infection

Cited by 19 publications

References 113 publications

Klebsiella pneumoniae Lipopolysaccharides Serotype O2afg Induce Poor Inflammatory Immune Responses Ex Vivo

Klebsiella pneumoniae Lipopolysaccharides Serotype O2afg Induce Poor Inflammatory Immune Responses Ex Vivo

The role of Toll-like receptor 9 in a murine model of Cryptococcus gattii infection

Immunomodulatory Role of Capsular Polysaccharides Constituents of Cryptococcus neoformans

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