Apoptosis is a finely programmed process of cell death in which cells silently dismantle and actively participate in several operations such as immune response, differentiation, and cell growth. It can be initiated by three main pathways: the extrinsic, the perforin granzyme, and the intrinsic that culminate in the activation of several proteins in charge of tearing down the cell. On the other hand, apoptosis represents an ordeal for pathogens that live inside cells and maintain a strong dependency with them; thus, they have evolved multiple strategies to manipulate host cell apoptosis on their behalf. It has been widely documented that diverse intracellular bacteria, fungi, and parasites can interfere with most steps of the host cell apoptotic machinery to inhibit or induce apoptosis. Indeed, the inhibition of apoptosis is considered a virulence property shared by many intracellular pathogens to ensure productive replication. Some pathogens intervene at an early stage by interfering with the sensing of extracellular signals or transduction pathways. Others sense cellular stress or target the apoptosis regulator proteins of the Bcl-2 family or caspases. In many cases, the exact molecular mechanisms leading to the interference with the host cell apoptotic cascade are still unknown. However, intense research has been conducted to elucidate the strategies employed by intracellular pathogens to modulate host cell death. In this review, we summarize the main routes of activation of apoptosis and present several processes used by different bacteria, fungi, and parasites to modulate the apoptosis of their host cells.

Entamoeba histolytica is the causative agent of amebiasis in humans and is responsible for 100,000 deaths annually, making it the third leading cause of death due to a protozoan parasite. Pathogenesis appears to result from the potent cytotoxic activity of the parasite, which kills host cells within minutes. Although the mechanism is unknown, it is well established to be contact-dependent. The life cycle of the parasite alternates with two forms: the resistant cyst and the invasive trophozoite. The adhesive interactions between the parasite and surface glycoconjugates of host cells, as well as those lining the epithelia, are determinants for invasion of human tissues, for its cytotoxic activity, and finally for the outcome of the disease. In this review we present an overview of the information available on the amebic lectins and adhesins that are responsible of those adhesive interactions and we also refer to their effect on the host immune response. Finally, we present some concluding remarks and perspectives in the field.

Dendritic cells (DCs) are a type of cells derived from bone marrow that represent 1% or less of the total hematopoietic cells of any lymphoid organ or of the total cell count of the blood or epithelia. Dendritic cells comprise a heterogeneous population of cells localized in different tissues where they act as sentinels continuously capturing antigens to present them to T cells. Dendritic cells are uniquely capable of attracting and activating naïve CD4⁺ and CD8⁺ T cells to initiate and modulate primary immune responses. They have the ability to coordinate tolerance or immunity depending on their activation status, which is why they are also considered as the orchestrating cells of the immune response. The purpose of this review is to provide a general overview of the current knowledge on ontogeny and subsets of human dendritic cells as well as their function and different biological roles.

There are many types of cell death, each involving multiple and complex molecular events. Cell death can occur accidentally when exposed to extreme physical, chemical, or mechanical conditions, or it can also be regulated, which involves a genetically coded complex machinery to carry out the process. Apoptosis is an example of the latter. Apoptotic cell death can be triggered through different intracellular signalling pathways that lead to morphological changes and eventually cell death. This is a normal and biological process carried out during maturation, remodelling, growth, and development in tissues. To maintain tissue homeostasis, regulatory, and inhibitory mechanisms must control apoptosis. Paradoxically, these same pathways are utilized during infection by distinct intracellular microorganisms to evade recognition by the immune system and therefore survive, reproduce and develop. In cancer, neoplastic cells inhibit apoptosis, thus allowing their survival and increasing their capability to invade different tissues and organs. The purpose of this work is to review the generalities of the molecular mechanisms and signalling pathways involved in apoptosis induction and inhibition. Additionally, we compile the current evidence of apoptosis modulation during cancer and Leishmania infection as a model of apoptosis regulation by an intracellular microorganism.

The maintenance of homeostasis in living systems requires the elimination of unwanted cells which is performed, among other mechanisms, by type I cell death or apoptosis. This type of programmed cell death involves several morphological changes such as cytoplasm shrinkage, chromatin condensation (pyknosis), nuclear fragmentation (karyorrhexis), and plasma membrane blebbing that culminate with the formation of apoptotic bodies. In addition to the maintenance of homeostasis, apoptosis also represents an important defense mechanism for cells against intracellular microorganisms. In counterpart, diverse intracellular pathogens have developed a wide array of strategies to evade apoptosis and persist inside cells. These strategies include the manipulation of signaling pathways involved in the inhibition of apoptosis where mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) play a key role. Leishmania is an intracellular protozoan parasite that causes a wide spectrum of diseases known as leishmaniasis. This parasite displays different strategies, including apoptosis inhibition, to down-regulate host cell defense mechanisms in order to perpetuate infection.