Methamphetamine Impairs IgG1-Mediated Phagocytosis and Killing of Cryptococcus neoformans by J774.16 Macrophage- and NR-9640 Microglia-Like Cells

Aslanyan, Lilit; Lee, Hiu H.; Ekhar, Vaibhav V.; Ramos, Raddy L.; Martinez, Luis R.

doi:10.1128/iai.00113-18

Cited by 15 publications

(14 citation statements)

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“…It is possible that the maintenance of B cells in the lungs and spleen is related to the accumulation of METH in these tissues and the sensitivity of other cells to the drug. METH induces apoptosis in macrophages ( Aslanyan et al, 2019 ) and T cells ( Potula et al, 2010 ). However, B cell viability in vitro is only affected by a significantly high METH concentration (100 μM) or four times the concentration (25 μM) used in our studies ( House et al, 1994 ).…”

Section: Discussionmentioning

confidence: 99%

“…METH has important implications on Ab production ( Wey et al, 2008 ; Martinez et al, 2009 ), phagocytic responses ( Mihu et al, 2015 ), and the fate of pathogens ( Aslanyan et al, 2019 ) during infection. In addition, Ab isotype might be critical in stimulating the phagocytic cell migration and antimicrobial effector functions.…”

Section: Discussionmentioning

confidence: 99%

“…METH induces a mixed protective Th1 and a detrimental Th2 immune response facilitating infection and disease ( Martinez et al, 2009 ). Moreover, METH exposure results in apoptosis in T lymphocytes ( Potula et al, 2010 ) and macrophages ( Aslanyan et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Methamphetamine Compromises the Adaptive B Cell-Mediated Immunity to Antigenic Challenge in C57BL/6 Mice

et al. 2021

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Methamphetamine (METH) is a substance of abuse that causes dysregulation of the innate and adaptive immunity in users. B cells are involved in the humoral component of the adaptive immunity by producing and secreting antibodies (Abs). METH modifies Ab production, although limited information on the impact of this psychostimulant on antigen (Ag)-specific humoral immune responses is available. Since T cell-dependent and T cell-independent Ags are involved in the activation of B lymphocytes, we explored the role of METH on humoral immunity to ovalbumin (OVA; T cell-dependent) and bacterial lipopolysaccharide (LPS; T cell-independent) in C57BL/6 mice. We demonstrated that METH extends the infiltration of B cells into pulmonary and splenic tissues 7 days post-Ag challenge. METH impairs Ab responses in the blood of animals challenged with OVA and LPS. Furthermore, METH diminishes the expression and distribution of IgM on B cell surface, suggesting a possible detrimental impact on users' humoral immunity to infection or autoimmunity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Methamphetamine Compromises the Adaptive B Cell-Mediated Immunity to Antigenic Challenge in C57BL/6 Mice

et al. 2021

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“…Binge doses of 260 to 1,000 mg produce 17 to 80 μM blood METH levels and levels in the micromolar range of hundreds in organs ( 64 ). Thus, we selected 2.5 to 10 mg of METH/kg of body weight/day to perform our in vivo experiments ( 24 ) and 25 μM METH to perform our in vitro experiments ( 65 ).…”

Section: Methodsmentioning

confidence: 99%

Understanding the Basis of METH Mouth Using a Rodent Model of Methamphetamine Injection, Sugar Consumption, and Streptococcus mutans Infection

Lee

Sudhakara

Desai

et al. 2021

mBio

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“METH mouth” is a common consequence of chronic methamphetamine (METH) use, resulting in tooth decay and painful oral tissue inflammation that can progress to complete tooth loss. METH reduces the amount of saliva in the mouth, promoting bacterial growth, tooth decay, and oral tissue damage. This oral condition is worsened by METH users’ compulsive behavior, including high rates of consumption of sugary drinks, recurrent tooth grinding, and a lack of frequent oral hygiene. Streptococcus mutans is a Gram-positive bacterium found in the oral cavity and associated with caries in humans. Hence, we developed a murine model of METH administration, sugar intake, and S. mutans infection to mimic METH mouth in humans and to investigate the impact of this drug on tooth colonization. We demonstrated that the combination of METH and sucrose stimulates S. mutans tooth adhesion, growth, and biofilm formation in vivo. METH and sucrose increased the expression of S. mutans glycosyltransferases and lactic acid production. Moreover, METH contributes to the low environmental pH and S. mutans sucrose metabolism, providing a plausible mechanism for bacterium-mediated tooth decay. Daily oral rinse treatment with chlorhexidine significantly reduces tooth colonization in METH- and sucrose-treated mice. Furthermore, human saliva inhibits S. mutans colonization and biofilm formation after exposure to either sucrose or the combination of METH and sucrose. These findings suggest that METH might increase the risk of microbial dental disease in users, information that may help in the development of effective public health strategies to deal with this scourge in our society. IMPORTANCE “METH mouth” is characterized by severe tooth decay and gum disease, which often causes teeth to break or fall out. METH users are also prone to colonization by cariogenic bacteria such as Streptococcus mutans. In addition, this oral condition is aggravated by METH users’ compulsive behavior, including the consumption of beverages with high sugar content, recurrent tooth grinding, and a lack of frequent oral hygiene. We investigated the effects of METH and sugar consumption on S. mutans biofilm formation and tooth colonization. Using a murine model of METH administration, sucrose ingestion, and oral infection, we found that the combination of METH and sucrose increases S. mutans adhesion and biofilm formation on the teeth of C57BL/6 mice. However, daily chlorhexidine-based oral rinse treatment reduces S. mutans tooth colonization. Similarly, METH has been associated with dry mouth or hyposalivation in users. Hence, we assessed the impact of human saliva on biofilm formation and demonstrated that surface preconditioning with saliva substantially reduces S. mutans biofilm formation. Our results are significant because to our knowledge, this is the first basic science study focused on elucidating the fundamentals of METH mouth using a rodent model of prolonged drug injection and S. mutans oral infection. Our findings may have important translational implications for the development of treatments for the management of METH mouth and more effective preventive public health strategies that can be applied to provide effective dental care for METH users in prisons, drug treatment centers, and health clinics.

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“…However, there is some evidence that illicit drug use alone or in conjunction with HIV, may also contribute to the development of cryptococcosis. Related to immunoglobulin defects, the use of methamphetamine (METH) has been shown to impair IgG-mediated phagocytosis and killing of cryptococcal cells in murine models while also facilitating intracellular replication [ 187 , 188 ]. In addition, murine models have also shown that METH enhances PC infection and dissemination to the CNS through alteration of cryptococcal virulence factors (e.g., capsule composition and capsule shedding) and by reducing the integrity of the host blood brain barrier [ 189 , 190 ].…”

Section: Associations Between Human Attributes and Cryptococcosismentioning

confidence: 99%

Associations between Cryptococcus Genotypes, Phenotypes, and Clinical Parameters of Human Disease: A Review

Montoya

Magwene

Perfect

2021

JoF

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The genus Cryptococcus contains two primary species complexes that are significant opportunistic human fungal pathogens: C. neoformans and C. gattii. In humans, cryptococcosis can manifest in many ways, but most often results in either pulmonary or central nervous system disease. Patients with cryptococcosis can display a variety of symptoms on a spectrum of severity because of the interaction between yeast and host. The bulk of our knowledge regarding Cryptococcus and the mechanisms of disease stem from in vitro experiments and in vivo animal models that make a fair attempt, but do not recapitulate the conditions inside the human host. To better understand the dynamics of initiation and progression in cryptococcal disease, it is important to study the genetic and phenotypic differences in the context of human infection to identify the human and fungal risk factors that contribute to pathogenesis and poor clinical outcomes. In this review, we summarize the current understanding of the different clinical presentations and health outcomes that are associated with pathogenicity and virulence of cryptococcal strains with respect to specific genotypes and phenotypes.

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Methamphetamine Impairs IgG1-Mediated Phagocytosis and Killing of Cryptococcus neoformans by J774.16 Macrophage- and NR-9640 Microglia-Like Cells

Cited by 15 publications

References 70 publications

Methamphetamine Compromises the Adaptive B Cell-Mediated Immunity to Antigenic Challenge in C57BL/6 Mice

Methamphetamine Compromises the Adaptive B Cell-Mediated Immunity to Antigenic Challenge in C57BL/6 Mice

Understanding the Basis of METH Mouth Using a Rodent Model of Methamphetamine Injection, Sugar Consumption, and Streptococcus mutans Infection

Associations between Cryptococcus Genotypes, Phenotypes, and Clinical Parameters of Human Disease: A Review

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