Alveolar macrophages and monocyte subpopulations during Plasmodium berghei NK65 experimental malaria-associated acute respiratory distress syndrome.

Alveolar macrophages (AM) and monocytes (MO) are myeloid cells that play a substantial role in the development and establishment of the innate and adaptive immune response. These cells are crucial for host defense against various pathogens, but their role in malaria is poorly understood. Here, we characterize the dynamics of AMs and recruited leukocytes subpopulations in the airways during experimental Plasmodium berghei NK65-NY (PbNK65). We show that PbNK65 infection induces an increased pulmonary vascular permeability that provides Ly6Clow MOs, neutrophils (NEU), CD4+ and CD8+ lymphocytes in the airways. This inflammatory environment resulted in an increase in the population and alteration of the activation state of the AMs. Taken together, the data presented provide new insights into airway inflammation associated with pulmonary malaria.

Development of chimeric protein as a multivalent vaccine for human Kinetoplastid infections: Chagas disease and leishmaniasis.

Leishmania spp. and Trypanosoma cruzi are parasitic kinetoplastids of great medical and epidemiological importance since they are responsible for thousands of deaths and disability-adjusted life-years annually, especially in low- and middle-income countries. Despite efforts to minimize their impact, current prevention measures have failed to fully control their spread. There are still no vaccines available. Taking into account the genetic similarity within the Class Kinetoplastida, we selected CD8+ T cell epitopes preserved among Leishmania spp. and T. cruzi to construct a multivalent and broad-spectrum chimeric polyprotein vaccine. In addition to inducing specific IgG production, immunization with the vaccine was able to significantly reduce parasite burden in the colon, liver and skin lesions from T. cruzi, L. infantum and L. mexicana challenged mice, respectively. These findings were supported by histopathological analysis, which revealed decreased inflammation in the colon, a reduced number of degenerated hepatocytes and an increased proliferation of connective tissue in the skin lesions of the corresponding T. cruzi, L. infantum and L. mexicana vaccinated and challenged mice. Collectively, our results support the protective effect of a polyprotein vaccine approach and further studies will elucidate the immune profile associated with this protection. Noteworthy, our results act as conceptual proof that a single multi-kinetoplastida vaccine can be used effectively to control different infectious etiologies, which in turn can have a profound impact on the development of a new generation of vaccines.