For a long time Leishmaniasis had been considered as a neglected tropical disease. Recently, it has become a priority in public health all over the world for different aspects such as geographic spread, number of population living at risk of infection as well as the potential lethality and/or the development of disfiguring lesions in the, respectively, visceral and tegumentary forms of the disease. As a result, several groups have been bending over this issue and many valuable data have been published. Nevertheless, parasite-host interactions are still not fully known and, consequently, we do not entirely understand the infection dynamics and parasite persistence. This knowledge may point targets for modulation or blockage, being very useful in the development of measures to interfere in the course of infection/ disease and to minimize the risks and morbidity. In the present review we will discuss some aspects of the Leishmania spp—mammalian host interaction in the onset of infection and after the clinical cure of the lesions. We will also examine the information already available concerning the parasite strategy to evade immune response mainly at the beginning of the infection, as well as during the parasite persistence. This knowledge can improve the conditions of treatment, follow-up and cure control of patients, minimizing the potential damages this protozoosis can cause to infected individuals.

The first formal description of the microbicidal activity of extracellular traps (ETs) containing DNA occurred in neutrophils in 2004. Since then, ETs have been identified in different populations of cells involved in both innate and adaptive immune responses. Much of the knowledge has been obtained from in vitro or ex vivo studies; however, in vivo evaluations in experimental models and human biological materials have corroborated some of the results obtained. Two types of ETs have been described—suicidal and vital ETs, with or without the death of the producer cell. The studies showed that the same cell type may have more than one ETs formation mechanism and that different cells may have similar ETs formation mechanisms. ETs can act by controlling or promoting the mechanisms involved in the development and evolution of various infectious and non-infectious diseases, such as autoimmune, cardiovascular, thrombotic, and neoplastic diseases, among others. This review discusses the presence of ETs in neutrophils, macrophages, mast cells, eosinophils, basophils, plasmacytoid dendritic cells, and recent evidence of the presence of ETs in B lymphocytes, CD4+ T lymphocytes, and CD8+ T lymphocytes. Moreover, due to recently collected information, the effect of ETs on COVID-19 is also discussed.

Leishmaniasis is a vector-borne infectious disease caused by different species of protozoa from the Leishmania genus. Classically, the disease can be classified into two main clinical forms: Visceral (VL) and Tegumentary (TL) leishmaniasis. TL is a skin/mucosal granulomatous disease that manifests mainly as cutaneous localized or disseminated ulcers, papules diffusely distributed, mucosal lesions or atypical lesions. Once the etiology of the infection is confirmed, treatment can take place, and different drugs can be administered. It has already been shown that, even when the scar is clinically evident, inflammation is still present in the native tissue, and the decrease of the inflammatory process occurs slowly during the 1st years after clinical healing. The maintenance of residual parasites in the scar tissue is also well documented. Therefore, it is no longer a surprise that, under some circumstances, therapeutic failure and/or lesion reactivation occurs. All over the years, an impressive amount of data on relapses, treatment resistance and lesion reactivation after healing has been collected, and several factors have been pointed out as having a role in the process. Different factors such as Leishmania species, parasite variability, Leishmania RNA virus 1, parasite load, parasite persistence, age, nutritional status, gender, co-morbidities, co-infection, pregnancy, immunosuppression, lesion duration, number and localization of lesions, drug metabolism, irregular treatment and individual host cellular immune response were described and discussed in the present review. Unfortunately, despite this amount of information, a conclusive understanding remains under construction. In addition, multifactorial influence cannot be discarded. In this context, knowing why leishmaniasis has been difficult to treat and control can help the development of new approaches, such as drugs and immunotherapy in order to improve healing maintenance. In this sense, we would like to highlight some of the findings that may influence the course of Leishmania infection and the therapeutic response, with an emphasis on TL.

Sporotrichosis is a subacute/chronic mycosis caused by dimorphic fungus of the genus Sporothrix. This mycosis may affect both human and domestic animals and in the last few years, the geographic dispersion and increase of sporotrichosis worldwide has been observed. The occurrence of cases related to scratching/bites of domestic felines have increased, characterizing the disease as predominantly a zoonosis. In humans, sporotrichosis mainly involves the cutaneous tegument of infected patients, but other tissues may also present the infection. The main forms of clinical presentation are lymphocutanous sporotrichosis (LC) and fixed sporotrichosis (F). Although less common, mucosal, cutaneous disseminated, and extracutaneous forms have also been described. Multiple factors from the fungus and host can play a role in driving the clinical evolution of sporotrichosis to benign or severe disease. In this review, we discuss the immunopathological aspects involved in human sporotrichosis. Putting together the two branches of knowledge—host immune response and fungal evading mechanisms—we may perceive new possibilities in understanding the fungus–host interaction in order to be in a position to go further in the control of sporotrichosis.

Neutrophil extracellular traps (NETs) have been described as a network of extracellular fibers composed by DNA, histones and various proteins/enzymes. Studies have demonstrated that NETs could be responsible for the trapping and elimination of a variety of infectious agents. In order to verify the presence of NETs in American tegumentary leishmaniasis (ATL) and their relationship with the presence of amastigotes we evaluated active cutaneous lesions of 35 patients before treatment by the detection of parasites, neutrophils (neutrophil elastase) and histones through immunohistochemistry and confocal immunofluorescence. Intact neutrophils could be detected in all ATL lesions. NETs were present in 27 patients (median 1.1; range from 0.1 to 23.5/mm²) with lesion duration ranging from one to seven months. NETs were in close proximity with neutrophils (r = 0.586; p = 0.0001) and amastigotes (r = 0.710; p = 0.0001). Two patterns of NET formation were detected: small homogeneously distributed networks observed in all lesions; and large structures that could be visualized at a lower magnification in lesions presenting at least 20% of neutrophils. Lesions presenting the larger NET formation showed high parasite detection. A correlation between NET size and the number of intact amastigotes was observed (p=0.02). As we detected an association between NET and amastigotes, our results suggest that neutrophil migration and NET formation could be stimulated and maintained by stimuli derived from the parasite burden/parasite antigen in the extracellular environment. The observation of areas containing only antigens not intermingled with NETs (elastase and histone) suggests that the involvement of these structures in the control of parasite burden is a dynamic process in which the formation of NETs is exhausted with the destruction of the parasites. Since NETs were also associated with granulomas, this trapping would favor the activity of macrophages in order to control the parasite burden.