Cryptococcus neoformans is an encapsulated yeast-like fungus capable of causing life threatening meningoencephalitis in patients with impaired immunity. This microbe primarily infects the host via inhalation but has the ability to disseminate to the central nervous system (CNS) either as a single cell or inside of macrophages. Upon traversing the blood brain barrier, C. neoformans has the capacity to form biofilm-like structures known as cryptococcomas. Hence, we will discuss the C. neoformans elements contributing to biofilm formation including the fungus’ ability to survive in the acidic environment of a macrophage phagosome and inside of the CNS. The purpose of this mini-review is to instill fresh interest in understanding the importance of biofilms on fungal pathogenesis.
Acinetobacter baumannii has emerged as an important etiological agent of hospital-related infections, especially nosocomial pneumonia. The virulence factors of this bacterium and their interactions with the cells and molecules of the immune system just recently began to be extensively studied. Here, we investigated the impact of alveolar macrophages on A. baumannii pneumonia using a mouse model of infection and a flexible tissue culture system. We hypothesized that depletion of macrophages would enhance sepsis and severity of A. baumannii disease. We showed that macrophages are important for modulating the antibacterial function of neutrophils and play an important role in eradicating A. baumannii infection in vivo. Our findings suggest that in the absence of macrophages in the lungs, A. baumannii replicates significantly, and host proinflammatory cytokines are considerably reduced. Neutrophils are abundantly recruited to pulmonary tissue, releasing high amounts of reactive oxygen species and causing extensive tissue damage. The ability of A. baumannii to form biofilms and resist oxidative stress in the respiratory tract facilitates systemic dissemination and ultimately death of infected C57BL/6 mice. These results provide novel information regarding A. baumannii pathogenesis and may be important for the development of therapies aimed at reducing morbidity and mortality associated with this emerging bacterial pathogen.
Methamphetamine (METH) is a powerful and highly addictive stimulant that affects the central nervous system of users in the United States and worldwide, and its consumption is associated to the acquisition of HIV and AIDS-related infections. METH enhances cryptococcosis in mice, an opportunistic infection caused by the encapsulated fungus Cryptococcus neoformans. Due to its ability to survive within macrophages, C. neoformans is an ideal model to study pathogen-macrophage interactions. METH abrogates normal macrophage function, which might contribute to the higher rate and more rapid progression of infections in drug abusers. Hence, we investigated the role of complement and specific IgM to C. neoformans capsular polysaccharide on the function of J774.16 macrophage-like cells after exposure to METH. We found that complement and IgM significantly promotes complement-mediated phagocytosis of C. neoformans by J774.16 cells in comparison to co-incubation with complement alone. IgM enhances the expression of complement receptor 3 on the surface macrophages treated with the drug. Also, IgM-increased macrophage phagocytosis of C. neoformans may be associated with upregulation of GTPase-RhoA, a key regulator of the actin polymerization signaling cascade. Fungal cells incubated with complement and IgM in the presence of METH demonstrated higher number of cells per aggregate, a possible explanation for their enhanced ingestion by phagocytes. IgM increased killing of yeast cells by macrophages by inhibiting the alkalization of the phagosome and stimulating the intracellular production of nitric oxide. Together, our findings suggest that IgM stimulates the effector functions of macrophages against opportunistic pathogens in the setting of drug abuse.
The prevalence of methamphetamine (METH) use is estimated at ∼35 million people worldwide, with over 10 million users in the United States. Chronic METH abuse and dependence predispose the users to participate in risky behaviors that may result in the acquisition of HIV and AIDS-related infections.Cryptococcus neoformansis an encapsulated fungus that causes cryptococcosis, an opportunistic infection that has recently been associated with drug users. METH enhancesC. neoformanspulmonary infection, facilitating its dissemination and penetration into the central nervous system in mice.C. neoformansis a facultative intracellular microorganism and an excellent model to study host-pathogen interactions. METH compromises phagocyte effector functions, which might have deleterious consequences on infection control. In this study, we investigated the role of METH in phagocytosis and antigen processing by J774.16 macrophage- and NR-9460 microglia-like cells in the presence of a specific IgG1 toC. neoformanscapsular polysaccharide. METH inhibits antibody-mediated phagocytosis of cryptococci by macrophages and microglia, likely due to reduced expression of membrane-bound Fcγ receptors. METH interferes with phagocytic cells’ phagosomal maturation, resulting in impaired fungal control. Phagocytic cell reduction in nitric oxide production during interactions with cryptococci was associated with decreased levels of tumor necrosis factor alpha (TNF-α) and lowered expression of Fcγ receptors. Importantly, pharmacological levels of METH in human blood and organs are cytotoxic to ∼20% of the phagocytes. Our findings suggest that METH abrogates immune cellular and molecular functions and may be deadly to phagocytic cells, which may result in increased susceptibility of users to acquire infectious diseases.
Context Concussions can cause cognitive impairment, somatic symptoms, and behavioral changes. Symptoms may vary in severity, depending on the degree of traumatic force. Due to the biomechanical nature of this trauma, cranial somatic dysfunctions may commonly be seen in patients with concussion. Objective To determine whether patients were more likely to have nonphysiologic cranial somatic dysfunctions than physiologic cranial somatic dysfunctions after sustaining a concussion. Methods College athletes who had a concussion based on the Immediate Post-Concussion Assessment and Cognitive test were evaluated by a physician within 1 week of the injury. Patients were evaluated for somatic dysfunctions of the cranium. Cranial somatic dysfunctions were documented; test scores and force vectors were compared with the type of strain pattern using SPSS, with P<.05 demonstrating statistical significance. Results Sixteen patients were included in the study: 10 with nonphysiologic cranial strain somatic dysfunctions and 6 with physiologic dysfunctions. Compared with lateral forces, forces of impact with anterioposterior vectors were associated 1.5 times more often with nonphysiologic rather than physiologic cranial somatic dysfunctions (P=.697). An analysis of specific cranial strain patterns and impact force vectors showed no statistical significance (P=.096). Conclusion There was no statistically significant association showing that concussion patients were more likely to have nonphysiologic cranial somatic dysfunctions compared with physiological cranial somatic dysfunctions. However, nonphysiologic cranial somatic dysfunctions did show a trend toward association with concussion. Further studies are needed to better understand the potential association between concussion and cranial somatic dysfunctions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.