Chromoblastomycosis (CBM) is a neglected human disease, caused by different species of pigmented dematiaceous fungi that cause subcutaneous infections. This disease has been considered an occupational disease, occurring among people working in the field of agriculture, particularly in low-income countries. In 1914, the first case of CBM was described in Brazil, and although efforts have been made, few scientific and technological advances have been made in this area. In the field of fungi and host cell relationship, a very reduced number of antigens were characterized, but available data suggest that ectoantigens bind to the cell membrane of host cells and modulate the phagocytic, immunological, and microbicidal responses of immune cells. Furthermore, antigens cleave extracellular proteins in tissues, allowing fungi to spread. On the contrary, if phagocytic cells are able to present antigens in MHC molecules to T lymphocytes in the presence of costimulation and IL-12, a Th1 immune response will develop and a relative control of the disease will be observed. Despite knowledge of the resistance and susceptibility in CBM, up to now, no effective vaccines have been developed. In the field of chemotherapy, most patients are treated with conventional antifungal drugs, such as itraconazole and terbinafine, but these drugs exhibit limitations, considering that not all patients heal cutaneous lesions. Few advances in treatment have been made so far, but one of the most promising ones is based on the use of immunomodulators, such as imiquimod. Data about a standard treatment are missing in the medical literature; part of it is caused by the existence of a diversity of etiologic agents and clinical forms. The present review summarizes the advances made in the field of CBM related to the diversity of pathogenic species, fungi and host cell relationship, antigens, innate and acquired immunity, clinical forms of CBM, chemotherapy, and diagnosis.

Cutaneous leishmaniasis exhibits a wide spectrum of clinical manifestations; however, only a limited number of drugs are available and include Glucantime^® and amphotericin B, which induce unacceptable side effects in patients, limiting their use. Thus, there is an urgent demand to develop a treatment for leishmaniasis. Recently, it was demonstrated that 8-hydroxyquinoline (8-HQ) showed significant leishmanicidal effects in vitro and in vivo. Based on that, this work aimed to develop a topical formulation containing 8-HQ and assess its activity in experimental cutaneous leishmaniasis. 8-HQ was formulated using a Beeler base at 1 and 2% and showed an emulsion size with a D₅₀ of 25 and 51.3 µm, respectively, with a shear-thinning rheological behaviour. The creams were able to permeate artificial Strat-M membranes and excised porcine skin without causing any morphological changes in the porcine skin or murine skin tested. In BALB/c mice infected with L. (L.) amazonensis, topical treatment with creams containing 1 or 2% of 8-HQ was found to reduce the parasite burden and lesion size compared to infected controls with comparable efficacy to Glucantime^® (50 mg/kg) administered at the site of the cutaneous lesion. In the histological section of the skin from infected controls, a diffuse inflammatory infiltrate with many heavily infected macrophages that were associated with areas of necrosis was observed. On the other hand, animals treated with both creams showed only moderate inflammatory infiltrate, characterised by few infected macrophages, while tissue necrosis was not observed. These histological characteristics in topically treated animals were associated with an increase in the amount of IFN-γ and a reduction in IL-4 levels. The topical use of 8-HQ was active in decreasing tissue parasitism and should therefore be considered an interesting alternative directed to the treatment of leishmaniasis, considering that this type of treatment is non-invasive, painless, and, importantly, does not require hospitalisation, improving patient compliance by allowing the treatment to be conducted.

The pathogenesis of chromoblastomycosis (CBM) is associated with Th2 and/or T regulatory immune responses, while resistance is associated with a Th1 response. However, even in the presence of IFN-γ, fungi persist in the lesions, and the reason for this persistence is unknown. To clarify the factors associated with pathogenesis, this study aimed to determine the polarization of the cellular immune response and the densities of cells that express markers of exhaustion in the skin of CBM patients. In the skin of patients with CBM, a moderate inflammatory infiltrate was observed, characterized primarily by the occurrence of histiocytes. Analysis of fungal density allowed us to divide patients into groups that exhibited low and high fungal densities; however, the intensity of the inflammatory response was not related to mycotic loads. Furthermore, patients with CBM exhibited a significant increase in the number of CD4⁺ and CD8⁺ cells associated with a high density of IL-10-, IL-17-, and IFN-γ-producing cells, indicating the presence of a chronic and mixed cellular immune response, which was also independent of fungal load. A significant increase in the number of PD-1⁺ and PD-L1⁺ cells was observed, which may be associated with the maintenance of the fungus in the skin and the progression of the disease.

Visceral leishmaniasis (VL) is one of the most severe clinical manifestations of leishmaniasis as it leads to death in 90% of untreated cases. The liver, spleen and bone marrows are the organs most affected; however, Leishmania parasites are able to reach the intestines where the gut-associated lymphoid tissue (GALT) is located. Under physiological conditions, the gastrointestinal tract and GALT interact with the enteric nervous system (SNE); however, there are no studies exploring the modulatory role of Leishmania (Leishmania) infantum in the intestines. Thus, this work aimed to investigate the parasitism, stratigraphy, and morphological changes in the myenteric plexus of golden hamsters infected with L. (L.) infantum. The animals were infected intraperitoneally, and the parasite load was evaluated in the spleen, the liver, and the jejunum. The stratigraphic evaluation and the quantitative and morphometric analyses of NADH-dp and NADPH-dp myenteric neurons were studied at 30-, 60-, and 90-days post-infection (DPI). Parasites in the spleen, the liver, and the jejunum increased during the progression of the infection. Stratigraphy studies showed a significant hypertrophy of the villi and the crypts associated with the increased intraepithelial lymphocytes that were observed in the jejunum of the infected animals. In addition, mucosal atrophy associated with a reduction in AB+ and PAS+ goblet cells was observed at 60 DPI and 90 DPI. These morphological changes were associated with an atrophy of the cell profile from NADPH-dp myenteric neurons. Furthermore, a significant decrease in the densities of this neuron population was observed in the chronic phase of the infection. This study suggests that L. (L.) infantum parasites are able to alter the morphology and innervation of the jejunum in golden hamsters.

Leishmaniasis is an infectious disease caused by several species of Leishmania parasites that preferentially infect macrophages as host cells. These intracellular parasites can evade the main microbicidal effector mechanisms of phagocytic cells and, in turn, are able to stimulate marked Th2 or regulatory T cell immune responses, which are not protective for the host. The presence of a non-protective immune response, together with the multiplication and spread of Leishmania parasites throughout the tissues, leads to the main clinical forms of leishmaniasis, such as cutaneous and visceral leishmaniasis. Although some clinical forms can be reproduced in experimental hosts such as mice and hamsters, these models do not fully mimic natural infection, which, in fact, impacts experimental vaccine development. For example, BALB/c mice are generally infected with around one million parasites, whereas humans are not infected with more than 1000 parasites, together with vector saliva. This excessive number of parasites in experimental models may affect the efficacy of vaccines in preclinical studies. Indeed, many experimental studies conducted over the past 20 years have shown only partial protection, regardless of the vaccine generation, host species employed, or the use of adjuvants. This review aims to summarize the main aspects associated with Leishmania vaccine development, including parasite diversity, host factors, immune responses, adjuvants, and antigens. Although many elegant studies have been conducted, it is possible that some essential step is still missing for the development of an effective vaccine for human use.