The Th2 Response and Alternative Activation of Macrophages Triggered by Strongyloides venezuelensis Is Linked to Increased Morbidity and Mortality Due to Cryptococcosis in Mice.

Cryptococcosis is a systemic mycosis that causes pneumonia and meningoencephalitis. Strongyloidiasis is a chronic gastrointestinal infection caused by parasites of the genus Strongyloides. Cryptococcosis and strongyloidiasis affect the lungs and are more prevalent in the same world regions, i.e., Africa and tropical countries such as Brazil. It is undeniable that those coincidences may lead to the occurrence of coinfections. However, there are no studies focused on the interaction between Cryptococcus spp. and Strongyloides spp. In this work, we aimed to investigate the interaction between Strongyloides venezuelensis (Sv) and Cryptococcus gattii (Cg) in a murine coinfection model. Murine macrophage exposure to Sv antigens reduced their ability to engulf Cg and produce reactive oxygen species, increasing the ability of fungal growth intracellularly. We then infected mice with both pathogens. Sv infection skewed the host's response to fungal infection, increasing lethality in a murine coinfection model. In addition to increased NO levels and arginase activity, coinfected mice presented a classic Th2 anti-Sv response: eosinophilia, higher levels of alternate activated macrophages (M2), increased concentrations of CCL24 and IL-4, and lower levels of IL-1ß. This milieu favored fungal growth in the lungs with prominent translocation to the brain, increasing the host's tissue damage. In conclusion, our data shows that primary Sv infection promotes Th2 bias of the pulmonary response to Cg-infection and worsens its pathological outcomes.

Late Diagnosis of Disseminated Sporothrix brasiliensis Infection with Bone Marrow Involvement in an HIV-Negative Patient.

Sporotrichosis is a fungal disease that causes symptoms similar to those of other infectious and non-infectious diseases, making diagnosis difficult and challenging. Here, we report a case of an HIV-negative patient presenting disseminated sporotrichosis with widespread cutaneous lesions mimicking pyoderma gangrenosum, with bone marrow infection, pancytopenia, and hemophagocytic syndrome. However, all the clinical manifestations and a bacterial coinfection delayed the request for a fungal diagnosis. Therefore, sporotrichosis should always be investigated in patients from endemic areas presenting with widespread cutaneous lesions associated with pancytopenia.

Saline stress affects the pH-dependent regulation of the transcription factor PacC in the dermatophyte Trichophyton interdigitale.

Fungal growth and development depend on adaptation to the particular pH of their environment. Ambient pH sensing implies the activation of the pacC signaling pathway, which then acts as a critical regulator for different physiological conditions. The PacC transcription factor may also be associated with the control of salt stress tolerance. In a pH-dependent manner, salinity stress is surpassed by changes in gene expression and coordinated activation of other signaling pathways, thus permitting survival in the challenging environment. In this study, we assessed the regulatory role of Trichophyton interdigitale PacC in response to pH variation and salinity stress. By employing gene expression analysis, we evaluated the influence of PacC in the modulation of salt stress-related genes, including the transcription factors crz1, egr2, and the MAP kinase hog1 in the dermatophyte T. interdigitale. In our analysis, we also included the evaluation of a potassium/sodium efflux P-type ATPase aiming to identify the role of PacC on its ion pumping activity. Here we demonstrated that salinity stress and buffered pH conditions might affect the pacC gene modulation in the dermatophyte T. interdigitale.

Infection of Human Macrophages by Leishmania infantum Is Influenced by Ecto-Nucleotidases.

Ecto-nucleotidase activity is involved in the infection process of Leishmania and various other parasites that enables modulation of host immune responses to promote disease progression. One of the enzymes responsible for this activity is the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase). The enzyme hydrolyzes nucleotides tri- and/or di-phosphate into monophosphate products, which are subsequently hydrolyzed into adenosine. These nucleotides can serve as purinergic signaling molecules involved in diverse cellular processes that govern immune responses. Given the importance of the extracellular metabolism of these nucleotides during intracellular pathogen infections, this study evaluates the role of ecto-nucleotidase activity during Leishmania infantum (L. infantum) infection in human macrophages. E-NTPDase protein expression and activity was evaluated in L. infantum during purine starvation, adenosine-enriched medium, or in the presence of an inhibitor of ecto-nucleotidases. Results show that E-NTPDase is expressed in L. infantum parasites, including on the cell membrane. Furthermore, functional activity of the enzyme was modulated according to the availability of adenosine in the medium. Purine starvation increased the hydrolytic capacity of nucleotides leading to higher infectivity, while growth in adenosine-enriched medium led to lower infectivity. Moreover, inhibiting E-NTPDase function decreased L. infantum infection in macrophages, suggesting the enzyme may serve as a ligand. Taken together, the ability of L. infantum to hydrolyze nucleotides is directly associated with increased infectivity in macrophages.

In vitro and ex vivo infection models help assess the molecular aspects of the interaction of Trichophyton rubrum with the host milieu.

Dermatophytes are fungal pathogens that cause cutaneous infections such as onychomycosis and athlete's foot in both healthy and immunocompromised patients.Trichophyton rubrum is the most prevalent dermatophyte causing human nail and skin infections worldwide, and because of its anthropophilic nature, animal infection models are limited. The purpose of this work was to compare the expression profile of T. rubrum genes encoding putative virulence factors during growth in ex vivo and in vitro infection models. The efficiency of the ex vivo skin infection model was confirmed by scanning electron microscopy (SEM), which showed that the conidia had produced hyphae that penetrated into the epidermis. Quantitative RT-PCR (qRT-PCR) analysis showed that the expression of some genes is modulated in response to the infection model used, as compared to that observed in cells grown in glucose-containing media. We concluded that ex vivo infection models help assess the molecular aspects of the interaction of T. rubrum with the host milieu, and thus provide insights into the modulation of genes during infection.