Staphylococcus aureus triggers a protective inflammatory response against secondary Cryptococcus gattii infection in a murine model

Emídio, Elúzia Castro Peres; Singulani, Júnya de Lacorte; Freitas, Gustavo José Cota de; Costa, Marliete Carvalho; Gouveia-Eufrásio, Ludmila; Carmo, Paulo Henrique Fonseca do; Pedroso, Silvia Helena Sousa Pietra; Brito, Camila Bernardo de; Bastos, Rafael Wesley; Ribeiro, Noelly Queiroz; Oliveira, Lorena; Silva, Monique Ferreira; Paixão, Tatiane Alves da; Souza, Daniele G.; Santos, Danielle Anjos dos

doi:10.1016/j.micinf.2023.105122

Cited by 3 publications

(2 citation statements)

References 27 publications

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“…After 3 days of Sp infection (7 days of Cg), mice were euthanized under anaesthesia, and lungs, liver, spleen, brain and BALF were collected. Tissues were homogenized in sterile PBS, plated on SDA and incubated for 48 h at 37 C to determine the fungal burden, expressed as CFU per gram or mL [15]. An aliquot of the same samples was plated on blood agar and incubated for 12 h at 37 C with 5% CO 2 to determine the bacteria burden [21].…”

Section: Fungal and Bacteria Burdenmentioning

confidence: 99%

“…Coinfections are infections caused by two or more microorganisms, which may present synergistically or sequentially [13,14].The problem in these conditions is that the first infection modifies immunity and pathology to the secondary one [13,[15][16][17][18]. For instance, previous infection by Influenza A virus facilitates the colonization and infection by both S. pneumoniae and C. gattii, contributing to the development of more severe infections [19,20].…”

Section: Introductionmentioning

confidence: 99%

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Secondary Streptococcus pneumoniae infection increases morbidity and mortality during murine cryptococcosis

Miranda,

Freitas,

Leocádio

et al. 2023

Immunology

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Microorganisms that cause pneumonia and translocate to the central nervous system (CNS) are responsible for high mortality worldwide. The fungus Cryptococcus gattii (Cg) and the bacteria Streptococcus pneumoniae (Sp) target the same infection organs. This study aimed to investigate the consequences of secondary Sp infection during murine cryptococcosis. Mice infected with Sp after Cg showed significantly increased lethality and a drop in scores of motor behaviour, neuropsychiatric status and autonomous function. Previous Cg infection favoured Sp multiplication in the lungs, causing intense inflammation and necrosis, with further increased bacterial translocation to the spleen, liver and brain. This phenotype was associated with increased platelet‐activating factor receptor (Pafr) gene expression, reduced M1 macrophage recruitment, and high levels of proinflammatory mediators. Strategies to overcome early mortality (i.e., infection of Pafr−/− mice, treatment with IL‐1 inhibitor or corticoid) were insufficient to revert this phenotype. These results suggest that Cg infection makes the lung microenvironment favourable for Sp colonization and dissemination. Altogether, it leads to an exacerbated and ineffective inflammatory response, decisive for the increased morbidity and mortality during coinfection. In conclusion, our results highlight the importance of more studies addressing coinfections and their consequences in the host, aiming to establish more effective therapeutical strategies.

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Section: Fungal and Bacteria Burdenmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Secondary Streptococcus pneumoniae infection increases morbidity and mortality during murine cryptococcosis

Miranda,

Freitas,

Leocádio

et al. 2023

Immunology

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Immune evasion by Cryptococcus gattii in vaccinated mice coinfected with C. neoformans

Hester,

Carlson,

Lodge

et al. 2024

Front. Immunol.

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Cryptococcus neoformans and C. gattii, the etiologic agents of cryptococcosis, cause over 100,000 deaths worldwide every year, yet no cryptococcal vaccine has progressed to clinical trials. In preclinical studies, mice vaccinated with an attenuated strain of C. neoformans deleted of three cryptococcal chitin deacetylases (Cn-cda1Δ2Δ3Δ) were protected against a lethal challenge with C. neoformans strain KN99. While Cn-cda1Δ2Δ3Δ extended the survival of mice infected with C. gattii strain R265 compared to unvaccinated groups, we were unable to demonstrate fungal clearance as robust as that seen following KN99 challenge. In stark contrast to vaccinated mice challenged with KN99, we also found that R265-challenged mice failed to induce the production of protection-associated cytokines and chemokines in the lungs. To investigate deficiencies in the vaccine response to R265 infection, we developed a KN99-R265 coinfection model. In unvaccinated mice, the strains behaved in a manner which mirrored single infections, wherein only KN99 disseminated to the brain and spleen. We expanded the coinfection model to Cn-cda1Δ2Δ3Δ-vaccinated mice. Fungal burden, cytokine production, and immune cell infiltration in the lungs of vaccinated, coinfected mice were indicative of immune evasion by C. gattii R265 as the presence of R265 neither compromised the immunophenotype established in response to KN99 nor inhibited clearance of KN99. Collectively, these data indicate that R265 does not dampen a protective vaccine response, but rather suggest that R265 remains largely undetected by the immune system.

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Preclinical Models for Cryptococcosis of the CNS and Their Characterization Using In Vivo Imaging Techniques

Roosen,

Maes,

Musetta

et al. 2024

JoF

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Infections caused by Cryptococcus neoformans and Cryptococcus gattii remain a challenge to our healthcare systems as they are still difficult to treat. In order to improve treatment success, in particular for infections that have disseminated to the central nervous system, a better understanding of the disease is needed, addressing questions like how it evolves from a pulmonary to a brain disease and how novel treatment approaches can be developed and validated. This requires not only clinical research and research on the microorganisms in a laboratory environment but also preclinical models in order to study cryptococci in the host. We provide an overview of available preclinical models, with particular emphasis on models of cryptococcosis in rodents. In order to further improve the characterization of rodent models, in particular the dynamic aspects of disease manifestation, development, and ultimate treatment, preclinical in vivo imaging methods are increasingly used, mainly in research for oncological, neurological, and cardiac diseases. In vivo imaging applications for fungal infections are rather sparse. A second aspect of this review is how research on models of cryptococcosis can benefit from in vivo imaging methods that not only provide information on morphology and tissue structure but also on function, metabolism, and cellular properties in a non-invasive way.

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Staphylococcus aureus triggers a protective inflammatory response against secondary Cryptococcus gattii infection in a murine model

Cited by 3 publications

References 27 publications

Secondary Streptococcus pneumoniae infection increases morbidity and mortality during murine cryptococcosis

Secondary Streptococcus pneumoniae infection increases morbidity and mortality during murine cryptococcosis

Immune evasion by Cryptococcus gattii in vaccinated mice coinfected with C. neoformans

Preclinical Models for Cryptococcosis of the CNS and Their Characterization Using In Vivo Imaging Techniques

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