Leishmaniasis is a parasitic, widespread, and neglected disease that affects more than 90 countries in the world. More than 20 Leishmania species cause different forms of leishmaniasis that range in severity from cutaneous lesions to systemic infection. The diversity of leishmaniasis forms is due to the species of parasite, vector, environmental and social factors, genetic background, nutritional status, as well as immunocompetence of the host. Here, we discuss the role of the immune system, its molecules, and responses in the establishment, development, and outcome of Leishmaniasis, focusing on innate immune cells and Leishmania major interactions.

Cryptococcosis is a disease caused by the pathogenic fungi Cryptococcus neoformans and Cryptococcus gattii, both environmental fungi that cause severe pneumonia and may even lead to cryptococcal meningoencephalitis. Although C. neoformans affects more fragile individuals, such as immunocompromised hosts through opportunistic infections, C. gattii causes a serious indiscriminate primary infection in immunocompetent individuals. Typically seen in tropical and subtropical environments, C. gattii has increased its endemic area over recent years, largely due to climatic factors that favor contagion in warmer climates. It is important to point out that not only C. gattii, but the Cryptococcus species complex produces a polysaccharidic capsule with immunomodulatory properties, enabling the pathogenic species of Cryptococccus to subvert the host immune response during the establishment of cryptococcosis, facilitating its dissemination in the infected organism. C. gattii causes a more severe and difficult-to-treat infection, with few antifungals eliciting an effective response during chronic treatment. Much of the immunopathology of this cryptococcosis is still poorly understood, with most studies focusing on cryptococcosis caused by the species C. neoformans. C. gattii became more important in the epidemiological scenario with the outbreaks in the Pacific Northwest of the United States, which resulted in phylogenetic studies of the virulent variant responsible for the severe infection in the region. Since then, the study of cryptococcosis caused by C. gattii has helped researchers understand the immunopathological aspects of different variants of this pathogen.

Malaria-associated acute respiratory distress syndrome (MA-ARDS) is a potentially lethal complication of clinical malaria. Acute lung injury in MA-ARDS shares features with ARDS triggered by other causes, including alveolar inflammation and increased alveolar-capillary permeability, leading to leak of protein-rich pulmonary oedema fluid. Mechanisms and physiologic alterations in MA-ARDS can be examined in murine models of this syndrome. Integrin αDβ2 is a member of the leukocyte, or β2 (CD18), sub-family of integrins, and emerging observations indicate that it has important activities in leukocyte adhesion, accumulation and signalling. The goal was to perform analysis of the lungs of mice wild type C57Bl/6 (a D +/+ ) and Knockout C57Bl/6 (a D −/− ) with malaria-associated acute lung injury to better determine the relevancy of the murine models and investigate the mechanism of disease. C57BL/6 wild type (a D +/+ ) and deficient for CD11d sub-unit (a D −/− ) mice were monitored after infection with 105 Plasmodium berghei ANKA. CD11d subunit expression RNA was measured by real-time polymerase chain reaction, vascular barrier integrity by Evans blue dye (EBD) exclusion and cytokines by ELISA. Protein and leukocytes were measured in bronchoalveolar lavage fluid (BALF) samples. Tissue cellularity was measured by the point-counting technique, F4/80 and VCAM-1 expression by immunohistochemistry. Respiratory function was analysed by non-invasive BUXCO and mechanical ventilation. Alveolar inflammation, vascular and interstitial accumulation of monocytes and macrophages, and disrupted alveolar-capillary barrier function with exudation of protein-rich pulmonary oedema fluid were present in P. berghei-infected wild type mice and were improved in αDβ2-deficient animals. Key pro-inflammatory cytokines were also decreased in lung tissue from α D −/− mice, providing a mechanistic explanation for reduced alveolar-capillary inflammation and leak. The results indicate that αDβ2 is an important inflammatory effector molecule in P. berghei-induced MA-ARDS, and that leukocyte integrins regulate critical inflammatory and pathophysiologic events in this model of complicated malaria. Genetic deletion of integrin subunit αD in mice, leading to deficiency of integrin αDβ2, alters lung inflammation and acute lung injury in a mouse model of MA-ARDS caused by P. berghei.

Parasite–host interactions depend on a complex interplay between the metabolism of the parasite, their antigens, and the host immune response system

Feline leishmaniasis is an emerging zoonotic disease, yet the cellular and immunological mechanisms underlying Leishmania infection in cats remain poorly understood. In this study, we established and characterized Fcwf-4 feline macrophages as an in vitro model of Leishmania amazonensis infection and investigated the immunomodulatory effects of glucuronoxylomannan (GXM), the major capsular polysaccharide of Cryptococcus neoformans. Fcwf-4 macrophages were infected with L. amazonensis promastigotes and evaluated at 2, 24, and 48 h post-infection. Parasite burden, macrophage viability, nitric oxide (NO), and reactive oxygen species (ROS) production were assessed in the presence or absence of GXM. Fcwf-4 macrophages supported L. amazonensis infection throughout the experimental period, with a progressive decrease in the infection index, indicating partial control of parasite burden over time. Notably, the presence of GXM increased the infection index without compromising macrophage viability, suggesting that enhanced parasite persistence resulted from immunomodulation rather than cytotoxicity. LPS stimulation enhanced NO and ROS production, whereas L. amazonensis infection selectively reduced NO production, indicating impairment of macrophage effector responses. Further, GXM suppressed ROS production, including basal ROS levels, suggesting an additional inhibitory effect on macrophage oxidative responses. Collectively, these findings provide experimental evidence that Fcwf-4 could be useful as a tool to study feline macrophage–Leishmania interactions in vitro and co-infection-associated immunomodulation.