Cryptococcal Infection with Ruxolitinib in Primary Myelofibrosis: A Case Report and Literature Review

Cryptococcus neoformans (CN) is an encapsulated yeast that causes disseminated and potentially life-threatening in immunocompromised hosts. We present a patient with primary myelofibrosis on ruxolitinib who developed disseminated disease due to CN. The report underscores the importance of suspecting infections with intracellular pathogens in immunosuppressed patients on ruxolitinib.

Phagosome maturation and modulation of macrophage effector function by intracellular pathogens: target for therapeutics

Macrophages are important cells that regulate various innate functions. Macrophages after engulfment of pathogens proceed for phagosome maturation and finally fuse with lysosomes to kill pathogens. Although pathogen degradation is one of the important functions of phagosomes, various immune-effector functions of macrophages are also dependent on the phagosome maturation process. This review discusses signaling processes regulating phagosome maturation as well as various effector functions of macrophages such as apoptosis, antigen presentation, autophagy and inflammasome that are dependent on the phagosome maturation process. It also discusses strategies adopted by various intracellular pathogens to counteract these functions to evade intracellular destruction mechanisms. These studies may give direction for the development of new therapeutics to control various intracellular infections.

Innate Lymphoid Cells in Response to Intracellular Pathogens: Protection Versus Immunopathology

Innate lymphoid cells (ILCs) are a heterogeneous group of cytokine-producing lymphocytes which are predominantly located at mucosal barrier surfaces, such as skin, lungs, and gastrointestinal tract. ILCs contribute to tissue homeostasis, regulate microbiota-derived signals, and protect against mucosal pathogens. ILCs are classified into five major groups by their developmental origin and distinct cytokine production. A recently emerged intriguing feature of ILCs is their ability to alter their phenotype and function in response to changing local environmental cues such as pathogen invasion. Once the pathogen crosses host barriers, ILCs quickly activate cytokine production to limit the spread of the pathogen. However, the dysregulated ILC responses can lead to tissue inflammation and damage. Furthermore, the interplay between ILCs and other immune cell types shapes the outcome of the immune response. Recent studies highlighted the important role of ILCs for host defense against intracellular pathogens. Here, we review recent advances in understanding the mechanisms controlling protective and pathogenic ILC responses to intracellular pathogens. This knowledge can help develop new ILC-targeted strategies to control infectious diseases and immunopathology.

HALLAZGO DE MÓRULAS COMPATIBLES CON ANAPLASMA PLATYS EN UN CANINO DE LA CIUDAD DE ESPERANZA

Anaplasma platys is a Gram-negative, intracellular obligate bacterium that is transmitted by Rhipicephalus sanguineus ticks and has been identified in most of the country. It is the causative agent of canine infectious cyclic thrombocytopenia. The objective of this work is to report the finding of morulae compatible with A. platys in the blood smear of a 10-year-old male Weimaraner canine who was treated at the Hospital de Salud Animal of the Facultad de Ciencias Veterinarias of the Universidad Nacional del Litoral, in the city of Esperanza. The case could not be followed up, because the patient died a few days after his first consultation. The detection of obligate intracellular pathogens in blood smears has low sensitivity and specificity, therefore confirmation of the causative agent must be performed using PCR. Due to the severity of the condition presented in this case, it is necessary to differentiate the presence of Ehrliquia canis and confirm the finding of A. platys using PCR. Current scientific evidence reveals that the zoonotic potential of A. platys is very low or nil.

Emerging technologies and infection models in cellular microbiology

The field of cellular microbiology, rooted in the co-evolution of microbes and their hosts, studies intracellular pathogens and their manipulation of host cell machinery. In this review, we highlight emerging technologies and infection models that recently promoted opportunities in cellular microbiology. We overview the explosion of microscopy techniques and how they reveal unprecedented detail at the host-pathogen interface. We discuss the incorporation of robotics and artificial intelligence to image-based screening modalities, biochemical mapping approaches, as well as dual RNA-sequencing techniques. Finally, we describe chips, organoids and animal models used to dissect biophysical and in vivo aspects of the infection process. As our knowledge of the infected cell improves, cellular microbiology holds great promise for development of anti-infective strategies with translational applications in human health.

In vitro antimalarial activity of inhibitors of the human GTPase Rac1

Malaria accounts for millions of cases and thousands of deaths every year. In the absence of an effective vaccine, drugs are still the most important tool in the fight against the disease. Plasmodium parasites developed resistance for all the classes of known antimalarial drugs. Thus, the search for antimalarial drugs with novel mechanisms of action is compelling. The human GTPase Rac1 plays a role in parasite invasion of the host cell in many intracellular pathogens. Also in Plasmodium falciparum , it was suggested an involvement of Rac1 both during the invasion process and parasite intracellular development. Aim of this work is to test a panel of Rac1 inhibitors as potential antimalarial drugs. Fourteen commercially available or newly synthesized inhibitors of Rac1 were tested for antimalarial activity. Among these, EHop-016 was the most effective against P. falciparum in vitro, with nanomolar IC 50 (138.8 ± 16.0 nM on the chloroquine-sensitive D10 strain and 321.5 ± 28.5 nM on the chloroquine-resistant W2 strain), and Selectivity Index of 37.8. EHop-016 did not inhibit parasite invasion of red blood cells but affected parasite growth inside them. Among the tested Rac1 inhibitors, EHop-016 showed a promising activity that raises attention on this class of molecules as potential antimalarials and deserves further investigation.