The role of macrophages in the susceptibility of Fc gamma receptor IIb deficient mice to Cryptococcus neoformans

Surawut, Saowapha; Ondee, Thunnicha; Taratummarat, Sujittra; Palaga, Tanapat; Pisitkun, Prapaporn; Chindamporn, Ariya; Leelahavanichkul, Asada

doi:10.1038/srep40006

Cited by 28 publications

(42 citation statements)

References 40 publications

(62 reference statements)

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“…Moreover, GXM-induced immunosuppression is mediated by direct interaction with Fc␥RIIB (51), highlighting the importance of Fc␥Rs in the regulation of immunity. Even though addition of MAb to GXM reverses GXM-induced immunosuppression by shifting recognition of the polysaccharide antigen from Fc␥RIIB to Fc␥RIIA, it is probable that METH upregulates the Fas ligand in macrophages and other antigen-presenting cells, thus promoting T cell apoptosis and inhibition of a protective cell-mediated immunity which is important for controlling cryptococcosis (52,53). Despite CytD's well-known inhibitory effect on the cell's cytoskeleton actin polymerization and a previous study showing its inhibition of internalization via Fc␥Rs in phagocytes (54), to our knowledge this is the first report showing that CytD lowers the expression of Fc␥Rs in macrophages.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…Survival analysis of FcGRIIb−/− and pristane mice was performed by housing 5 female mice per cage for 15 months before sacrifice. Since lupus characteristics demonstrated as early as 20 wks post-pristane injection 7 and in 24-wk-old FcGRIIb−/− mice 5,19 , pristane (Sigmaaldrich, St. Louis, MO, USA) (0.5 ml) was administered in 4-wk-old WT mice to induce lupus approximately at 24-wk-old to match with FcGRIIb−/− mice. Due to age-dependent lupus characteristics in both lupus models, mice at 8-and 24-wk-old were used as representatives of asymptomatic and symptomatic lupus, respectively.…”

Section: Methodsmentioning

confidence: 99%

Leaky-gut enhanced lupus progression in the Fc gamma receptor-IIb deficient and pristane-induced mouse models of lupus

Thim-Uam

Surawut

Issara-Amphorn

et al. 2020

Sci Rep

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102

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The influence of gut-leakage or gut-microbiota upon lupus progression was explored in 2 lupus mouse models. Pristane, administered in 4-wk-old wild-type (WT) female mice, induced lupus characteristics at 24-wk-old similar to the lupus-onset in FcGRIIb−/− mice. Gut-microbiota alteration was induced by co-housing together with the gavage of feces from 40-wk-old FcGRIIb−/− mice (symptomatic lupus). On the other hand, gut-leakage was induced by dextran sulfate solution (DSS). DSS and gutmicrobiota alteration induced high serum anti-dsDNA immunoglobulin (Ig) as early as 30 days post-DSS only in FcGRIIb−/− mice. DSS, but not gut-microbiota alteration, enhanced lupus characteristics (serum creatinine and proteinuria) in both lupus models (but not in WT) at 60 days post-DSS. Indeed, DSS induced the translocation of molecular components of gut-pathogens as determined by bacterial burdens in mesenteric lymph node (MLN), endotoxemia (gut-bacterial molecule) and serum (1→3)-β-Dglucan (BG) (gut-fungal molecule) as early as 15 days post-DSS together with enhanced MLN apoptosis in both WT and lupus mice. However, DSS induced spleen apoptosis in FcGRIIb−/− and Wt mice at 30 and 60 days post-DSS, respectively, suggesting the higher impact of gut-leakage against spleen of lupus mice. In addition, macrophages preconditioning with LPS plus BG were susceptible to starvationinduced apoptosis, predominantly in FcGRIIb−/− cell, implying the influence of gut-leakage upon cell stress. in summary, gut-leakage induced gut-translocation of organismal-molecules then enhanced the susceptibility of stress-induced apoptosis, predominantly in lupus. Subsequently, the higher burdens of apoptosis in lupus mice increased anti-dsDNA Ig and worsen lupus severity through immune complex deposition. Hence, therapeutic strategies addressing gut-leakage in lupus are interesting.Systemic lupus erythematosus (SLE) is a common autoimmune disease with multi-organ involvement 1 . Fc gamma receptor IIb (FcGRIIb) dysfunction polymorphism associates with SLE, particularly in Asian populations 2 , possibly due to malaria-based selection pressure 3 . Indeed, the overexpression of FcGRIIb, either in autoimmune-prone mouse strains or wild-type (WT) animals, heightened the threshold for induction of autoimmune disease 4 . The defects of FcGRIIb, the only inhibitory receptor in FcGR family, induce exaggerated immune responses and cause lupus 5 . As such, FcGRIIb−/− mouse is an established lupus mouse model with lupus characteristics as early as 20-24 wks old and develops full-blown lupus after 32-40 wks old 5,6 . In parallel, a single peritoneal injection creatinine index (UPCI; detail later) and serum anti-dsDNA immunoglobulin (Ig) before the further experiments. Symptomatic lupus was defined as increased serum anti-dsDNA Ig together with high level of UPCI and/ or serum Cr in comparison with age-matched control WT mice.Dextran sulfate solution (DSS) induced gut-leakage and co-housing with fecal gavage for gut microbiota alteration. Dextran sulfate solution (DSS) (Sigm...

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Section: Methodsmentioning

confidence: 99%

“…Lupus characteristics were analyzed as per the protocol in previous publication ( Surawut et al, 2017 ). In brief, serum anti-dsDNA measurement was based on the ELISA assay of calf DNA (Invitrogen, Carlsbad, CA, United States) coated on 96-well plates ( Surawut et al, 2017 ). Urine protein creatinine index (UPCI), a representative of 24 h proteinuria, was determined by the equation; spot urine protein/spot urine creatinine ( Leelahavanichkul et al, 2010 ).…”

Section: Methodsmentioning

confidence: 99%

Helicobacter pylori Infection Increased Anti-dsDNA and Enhanced Lupus Severity in Symptomatic FcγRIIb-Deficient Lupus Mice

et al. 2018

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The defect on Fc gamma receptor IIb (FcγRIIb), the only inhibitory FcγR, has been identified as one of the genetic factors increasing susceptibility to lupus. The prevalence of Helicobacter pylori (HP) and FcγRIIb dysfunction-polymorphisms are high among Asians, and their co-existence is possible. Unfortunately, the influence of HP against lupus progression in patients with lupus is still controversial. In this study, the interactions between these conditions were tested with HP infection in 24-week-old FcγRIIb-/- mice (symptomatic lupus). HP induced failure to thrive, increased stomach bacterial burdens and stomach injury (histology and cytokines) in both wild-type and FcγRIIb-/- mice. While the severity of HP infection, as determined by these parameters, was not different between both strains, antibodies production (anti-HP, anti-dsDNA and serum gammaglobulin) were higher in FcγRIIb-/- mice compared to wild-type. Accordingly, HP infection also accelerated the severity of lupus as determined by proteinuria, serum creatinine, serum cytokines, renal histology, and renal immune complex deposition. Although HP increased serum cytokines in both wild-type and FcγRIIb-/- mice, the levels were higher in FcγRIIb-/- mice. As such, HP also increased spleen weight and induced several splenic immune cells responsible for antibody productions (activated B cell, plasma cell and follicular helper T cell) in FcγRIIb-/- mice, but not in wild-type. These data describe the different systemic responses against localized HP infection from diverse host genetic background. In conclusion, the mutual interactions between HP and lupus manifestations of FcγRIIb-/-mice were demonstrated in this study. With the prominent immune responses from the loss of inhibitory signaling in FcγRIIb-/- mice, HP infection in these mice induced intense chronic inflammation, increased antibody production, and enhanced lupus severity. Thus, the increased systemic inflammatory responses due to localized HP inducing gastritis in some patients with lupus may enhance lupus progression. More studies are needed.

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The role of macrophages in the susceptibility of Fc gamma receptor IIb deficient mice to Cryptococcus neoformans

Cited by 28 publications

References 40 publications

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

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

Leaky-gut enhanced lupus progression in the Fc gamma receptor-IIb deficient and pristane-induced mouse models of lupus

Helicobacter pylori Infection Increased Anti-dsDNA and Enhanced Lupus Severity in Symptomatic FcγRIIb-Deficient Lupus Mice

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