Unraveling the susceptibility of paracoccidioidomycosis: Insights towards the pathogen-immune interplay and immunogenetics

Cezar-dos-Santos, Fernando; Assolini, João Paulo; Okuyama, Nádia Calvo Martins; Viana, Kelvinson Fernandes; Oliveira, Karen Brajão de; Itano, Eiko Nakagawa

doi:10.1016/j.meegid.2020.104586

Cited by 7 publications

(8 citation statements)

References 165 publications

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“…However, systemic spreading with severe clinical manifestations has been correlated with intrinsic genetic characteristics of hosts, such as primary immunodeficiencies and individual lifestyle such as smoking, alcohol abuse, malnutrition, and treatment with immunosuppressive drugs [29,30]. Despite the extensive literature about the importance of innate immunity in the acute host response to infection and fungal control, the role of iNKT cells remains unknown [31]. To determine the impact of invariant Natural Killer T cells in P. brasiliensis infection, we used animals that lack the CD1d molecule, which are deficient in diverse CD1d-restricted cells, or the Jα281 TCR gene segment (Jα18 -/-), which results in the specific depletion of the iNKT phenotype [13,23].…”

Section: Discussionmentioning

confidence: 99%

Invariant Natural Killer T Cells as Key Players in Host Resistance against Paracoccidioides brasiliensis

Nogueira‐Neto

Loures

Schanoski

et al. 2021

Journal of Immunology Research

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Invariant Natural Killer T (iNKT) cells are key players in the immunity to several pathogens; however, their involvement in the resistance to Paracoccidioides brasiliensis infection remains unknown. Using splenocytes from CD1d (CD1d-/-) and iNKT-deficient (Jα18-/-) mice, we found that iNKT cells are the innate source of IFN-γ after P. brasiliensis infection and are required to potentiate macrophage oxidative burst and control fungal growth. To determine whether iNKT cells contribute in vivo to host resistance against P. brasiliensis infection, we infected intratracheally wild-type and Jα18-/- C57BL/6 mouse strains with the virulent Pb18 isolate. iNKT cell deficiency impaired the airway acute inflammatory response, resulting in decreased airway neutrophilia and reduced IFN-γ, KC, and nitric oxide (NO) production. The deficient innate immune response of Jα18-/- mice to Pb18 infection resulted in increased fungal burden in the lungs and spleen. Besides, the activation of iNKT cells in vivo by administration of the exogenous iNKT ligand α-galactosylceramide (α-GalCer) improved host resistance to P. brasiliensis infection. Although the mechanisms responsible for this phenomenon remain to be clarified, α-GalCer treatment boosted the local inflammatory response and reduced pulmonary fungal burden. In conclusion, our study is the first evidence that iNKT cells are important for the protective immunity to P. brasiliensis infection and their activation by an exogenous ligand is sufficient to improve the host resistance to this fungal infection.

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Section: Discussionmentioning

confidence: 99%

Invariant Natural Killer T Cells as Key Players in Host Resistance against Paracoccidioides brasiliensis

Nogueira‐Neto

Loures

Schanoski

et al. 2021

Journal of Immunology Research

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“…Furthermore, the MHC-II binding predictions from IEDB are available with seven alleles (DRB1*03:01, DRB1*07:01, DRB1*15:01, DRB3*01:01, DRB3*02:02, DRB4*01:01, DRB5*01:01), which have the best results in the definition of the IEDB consensus percentile rank [ 181 ]. In the context of systemic mycosis, it is important to point out that several studies have demonstrated the influence of HLA genes on the susceptibility of infections, highlighting the importance of certain alleles in the analysis [ 182 ]. The other point is the choice of the prediction method, which is more difficult because currently there are several online tools can be used to predict the T cell epitope [ 183 ].…”

Section: Bioinformatic Tools For Vaccine Development Against Fungimentioning

confidence: 99%

Fungal Vaccine Development: State of the Art and Perspectives Using Immunoinformatics

Inácio

Moreira

Cruz-Leite

et al. 2023

JoF

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Fungal infections represent a serious global health problem, causing damage to health and the economy on the scale of millions. Although vaccines are the most effective therapeutic approach used to combat infectious agents, at the moment, no fungal vaccine has been approved for use in humans. However, the scientific community has been working hard to overcome this challenge. In this sense, we aim to describe here an update on the development of fungal vaccines and the progress of methodological and experimental immunotherapies against fungal infections. In addition, advances in immunoinformatic tools are described as an important aid by which to overcome the difficulty of achieving success in fungal vaccine development. In silico approaches are great options for the most important and difficult questions regarding the attainment of an efficient fungal vaccine. Here, we suggest how bioinformatic tools could contribute, considering the main challenges, to an effective fungal vaccine.

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“…The host-parasite interactions in PCM and the consequent inflammatory responses of the body can lead to changes in hematological cells, such as anemia, leukocytosis, and eosinophilia [8]. These findings are more commonly reported in the acute/subacute form of the disease [9,10]. The production of cytokines has been implicated in these hematological alterations.…”

Section: Introductionmentioning

confidence: 99%

Analysis and Interpretation of Automated Blood Count in the Treatment of Chronic Paracoccidioidomycosis

Brito,

França,

Siqueira

et al. 2024

JoF

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Blood count is crucial for assessing bone marrow’s cell production and differentiation during infections, gaging disease severity, and monitoring therapeutic responses. The profile of blood count in chronic forms of paracoccidioidomycosis (PCM) has been insufficiently explored. To better understand the changes in hematological cells in different stages of the PCM chronic form, we evaluated the blood count, including immature blood cells in automated equipment, before and during the treatment follow-up of 62 chronic PCM patients. Predominantly male (96.8%) with an average age of 54.3 (standard deviation SD 6.9) years, participants exhibited pre-treatment conditions such as anemia (45.2%), monocytosis (38.7%), and leukocytosis (17.7%), which became less frequent after clinical cure. Anemia was more prevalent in severe cases. Notably, hemoglobin and reticulocyte hemoglobin content increased, while leukocytes, monocytes, neutrophils, immature granulocytes, and platelets decreased. Chronic PCM induced manageable hematological abnormalities, mainly in the red blood series. Monocytosis, indicating monocytes’ role in PCM’s immune response, was frequent. Post-treatment, especially after achieving clinical cure, significant improvements were observed in various hematological indices, including immature granulocytes and reticulocyte hemoglobin content, underscoring the impact of infection on these parameters.

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Unraveling the susceptibility of paracoccidioidomycosis: Insights towards the pathogen-immune interplay and immunogenetics

Cited by 7 publications

References 165 publications

Invariant Natural Killer T Cells as Key Players in Host Resistance against Paracoccidioides brasiliensis

Invariant Natural Killer T Cells as Key Players in Host Resistance against Paracoccidioides brasiliensis

Fungal Vaccine Development: State of the Art and Perspectives Using Immunoinformatics

Analysis and Interpretation of Automated Blood Count in the Treatment of Chronic Paracoccidioidomycosis

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