Diabetes alters immune response patterns to acute melioidosis in humans

Kronsteiner, Barbara; Chaichana, Panjaporn; Sumonwiriya, Manutsanun; Jenjaroen, Kemajittra; Chowdhury, Fazle Rabbi; Chumseng, Suchintana; Teparrukkul, Prapit; Limmathurotsakul, Direk; Npj., Day; Klenerman, Paul; Dunachie, Susanna

doi:10.1002/eji.201848037

Cited by 43 publications

(57 citation statements)

References 63 publications

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“…To date, host immune responses by CD4 T cells in HIV-positive persons with melioidosis remain unknown. Host immune responses during acute melioidosis associated with survival have been shown to be dominated by CD8 T and NK cells (36,37), and some redundancy may occur to allow compensation of low CD4 counts in HIV.…”

Section: Discussionmentioning

confidence: 99%

Human Immune Responses to Melioidosis and Cross-Reactivity to Low-Virulence Burkholderia Species, Thailand1

Rongkard¹,

Kronsteiner²,

Hantrakun³

et al. 2020

Emerg. Infect. Dis.

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Section: Discussionmentioning

confidence: 99%

Human Immune Responses to Melioidosis and Cross-Reactivity to Low-Virulence Burkholderia Species, Thailand1

Rongkard¹,

Kronsteiner²,

Hantrakun³

et al. 2020

Emerg. Infect. Dis.

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“…However, Buddhisa et al have demonstrated that in patients with T2DM the expression of programmed cell death ligand 1 (PD-L1) on the surface of B. pseudomallei infected neutrophils is increased thus impairing T cell function ( 230 ). Kronsteiner et al, have demonstrated that CD3 + CD4 − CD8 − double-negative T cells and antibodies are important for the survival of diabetic melioidosis patients, while the survival of non-diabetics relies on CD8 + T cells and NK cells ( 231 ). They also indicated that IFN-γ release from γδ T-cells have an important role in the induction of protective immune responses in diabetic patients.…”

Section: Effects Of T2dm On the Susceptibility Of Patients To Infectimentioning

confidence: 99%

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

et al. 2020

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Metabolic abnormalities such as dyslipidemia, hyperinsulinemia, or insulin resistance and obesity play key roles in the induction and progression of type 2 diabetes mellitus (T2DM). The field of immunometabolism implies a bidirectional link between the immune system and metabolism, in which inflammation plays an essential role in the promotion of metabolic abnormalities (e.g., obesity and T2DM), and metabolic factors, in turn, regulate immune cell functions. Obesity as the main inducer of a systemic low-level inflammation is a main susceptibility factor for T2DM. Obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. Hyperglycemia and the subsequent inflammation are the main causes of micro-and macroangiopathies in the circulatory system. They also promote the gut microbiota dysbiosis, increased intestinal permeability, and fatty liver disease. The impaired immune system together with metabolic imbalance also increases the susceptibility of patients to several pathogenic agents such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, the need for a proper immunization protocol among such patients is granted. The focus of the current review is to explore metabolic and immunological abnormalities affecting several organs of T2DM patients and explain the mechanisms, whereby diabetic patients become more susceptible to infectious diseases.

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“…The essential role of IFN-γ in the early control of melioidosis has been indicated by murine in vitro and in vivo experiments as well as in clinical studies [ 41 ]. Blocking of IFN-γ in a melioidosis mouse model led to a drastically reduced LD50 and increased the bacterial burden in spleen and liver [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Burkholderia pseudomallei triggers canonical inflammasome activation in a human primary macrophage-based infection model

et al. 2020

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Most of the current knowledge on Burkholderia pseudomallei -induced inflammasome activation and cell death in macrophages is derived from murine systems. Little is known about the involved bacterial structures and mechanisms in primary human macrophages. This is of particular relevance since murine and human macrophages as well as primary cells and cell lines differ in many aspects of inflammasome activation, including the proteins involved in the recognition of bacterial patterns. In this study, we therefore aimed (i) to establish an in vitro B . pseudomallei infection model with human monocyte-derived primary macrophages from single donors as these cells more closely resemble macrophages in the human host and (ii) to analyze B . pseudomallei -triggered cell death and bacterial elimination in those cells. Our results show that B . pseudomallei- infected primary human macrophages not only release the inflammasome-independent pro-inflammatory cytokines IL-8 and TNF-α, but are also engaged in canonical inflammasome activation as evidenced by caspase-1 and gasdermin D processing. Absence of the B . pseudomallei T3SS-3 needle protein BsaL, a potent activator of the canonical inflammasome, abolished lytic cell death, reduced IL-1β release, and caspase-1 and gasdermin D processing. IFN-γ, known to promote non-canonical inflammasome activation, did not influence pyroptosis induction or IL-1β release from infected primary human macrophages. Nevertheless, it reduced intracellular B . pseudomallei loads, an effect which was partially antagonist by the inhibition of NADPH oxidase. Overall, our data implicate T3SS-3 dependent inflammasome activation and IFN-γ induced immune mechanisms as critical defense mechanisms of human macrophages against B . pseudomallei . In addition, our infection model provides a versatile tool to study human host-pathogen interactions and has the potential to elucidate the role of human individual genetic variations in B . pseudomallei infections.

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Diabetes alters immune response patterns to acute melioidosis in humans

Cited by 43 publications

References 63 publications

Human Immune Responses to Melioidosis and Cross-Reactivity to Low-Virulence Burkholderia Species, Thailand1

Human Immune Responses to Melioidosis and Cross-Reactivity to Low-Virulence Burkholderia Species, Thailand1

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

Burkholderia pseudomallei triggers canonical inflammasome activation in a human primary macrophage-based infection model

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