Plasmacytoid dendritic cell bactericidal activity against Burkholderia pseudomallei

Williams, Natasha L.; Morris, Jodie L.; Rush, Catherine M.; Ketheesan, Natkunam

doi:10.1016/j.micinf.2014.12.007

Cited by 12 publications

(7 citation statements)

References 24 publications

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“…I, Supporting Information Table ) and concomitantly increased CD86 expression (data not shown) in died compared to survived non‐DM patients. Such an inverse relationship of reduced MHC‐II and increased CD86 expression has been previously observed in murine pDC infected with BP . Since HLA‐DR is known to be downregulated in the presence of IL‐10 , we sought to determine IL‐10 levels in serum of acute melioidosis patients.…”

Section: Resultsmentioning

confidence: 71%

Diabetes alters immune response patterns to acute melioidosis in humans

et al. 2019

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Diabetes mellitus (DM) is a serious global health problem currently affecting over 450 million people worldwide. Defining its interaction with major global infections is an international public health priority. Melioidosis is caused by Burkholderia pseudomallei, an exemplar pathogen for studying intracellular bacterial infection in the context of DM due to the 12‐fold increased risk in this group. We characterized immune correlates of survival in peripheral blood of acute melioidosis patients with and without DM and highlight different immune response patterns. We demonstrate the importance of circulating NK cells and show that CX3CR1 expression on lymphocytes is a novel correlate of survival from acute melioidosis. Furthermore, excessive serum levels of IL‐15 and IL‐18BP contribute to poor outcome independent of DM comorbidity. CD8+ T cells and granzyme B expression in NK cells are important for survival of non‐DM patients, whereas high antibody titers against B. pseudomallei and double‐negative T cells are linked to survival of DM patients. Recall responses support a role of γδ T‐cell‐derived IFN‐γ in the establishment of protective immunity in the DM group. Defining the hallmarks of protection in people with DM is crucial for the design of new therapies and vaccines targeting this rapidly expanding risk group.

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Section: Resultsmentioning

confidence: 71%

Diabetes alters immune response patterns to acute melioidosis in humans

et al. 2019

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“…pDCs are an important source of type I IFNs and a major initial source of IFNα: their early removal during viral infection delays antiviral immunity while in a murine model of lupus similar removal reduces the disease [ 2 , 18 ]. In addition, pDCs are involved in the immune response to bacterial pathogens, including both extracellular and intracellular organisms [ 19 – 21 ]. Given their contribution to other viral and bacterial infections and their involvement in other autoimmune and inflammatory diseases, we examined whether pDCs play a role in S .…”

Section: Resultsmentioning

confidence: 99%

Type I interferon signaling restrains IL-10R+ colonic macrophages and dendritic cells and leads to more severe Salmonella colitis

et al. 2017

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Type I interferons (IFNα, IFNβ) are key regulators of innate and adaptive immunity, modulating the severity of both viral and bacterial infections. While type I IFN signaling leads to improved outcomes in viral infections, its role in bacterial infections is more contextual and depends on the specific pathogen and route of infection. Given the limited evidence on whether type I IFN signaling affects enteric bacterial pathogens, we investigated the role of this signaling pathway in Salmonella enterica serovar Typhimurium (S. typhimurium)–induced colitis. Comparing mice deficient in IFNAR1- the common receptor for IFNα and IFNβ- with wild-type mice, we found that type I IFN signaling leads to more rapid death, more severe colonic inflammation, higher serum levels of pro-inflammatory cytokines, and greater bacterial dissemination. Specific ablation of plasmacytoid dendritic cells (pDCs), which are prominent producers of type I IFNs in antiviral responses, did not alter survival after infection. This result established that pDCs do not play a major role in the pathogenesis of S. typhimurium colitis. Flow cytometric analysis of macrophages and conventional dendritic cells (cDCs) during active colitis demonstrated an increase in CD11c- macrophages and CD103+ cDCs in the colon of Ifnar1-/- animals. Interestingly, cells expressing the anti-inflammatory cytokine receptor IL-10R are more abundant within these subsets in Ifnar1-/- than in wild-type mice. Moreover, blockade of IL-10R in Ifnar1-/- mice increased their susceptibility to S. typhimurium colitis, suggesting that altered numbers of these immunoregulatory cells may underlie the difference in disease severity. This cross-talk between type I IFN and IL-10R signaling pathways may represent a key host cellular mechanism to investigate further in order to unravel the balance between pathogenic inflammation and homeostasis of the colon. Taken together, our data clearly demonstrate that type I IFN signaling is pathogenic in S. typhimurium colitis.

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“…The gastrointestinal mucosa is a unique microenvironment wherein pDCs must distinguish pathogen-associated danger signals from signals associated with resident commensal microflora [ 47 ]. Inasmuch as pDCs themselves have direct bactericidal activity [ 48 ] and serve as biological bridges between innate and adaptive immunity, we examined how aging affects the migration of intestinal pDCs, alterations thereof could help explain reduced efficiency of mucosal immunity with aging [ 1 ]. Here, we adopted the classic LPS endotoxemia model that had been employed previously to show the role of pDC in conventional mucosal immunity in young adult mice [ 38 ].…”

Section: Discussionmentioning

confidence: 99%