MyD88-Dependent Recruitment of Monocytes and Dendritic Cells Required for Protection from Pulmonary Burkholderia mallei Infection

Goodyear, Andrew; Troyer, Ryan M.; Bielefeldt‐Ohmann, Helle; Dow, Steven

doi:10.1128/iai.05819-11

Cited by 16 publications

(17 citation statements)

References 38 publications

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“…This is in line with the report showing helminth-induced IL-4 and IL-13 responses suppressed neutrophil infiltration and pro-inflammatory cytokine responses during Schistosomiasis japonica infection in mice [38]. Recent evidence showed MyD88-dependent recruitment of MNP to lungs is required for protection against B. mallei infection [40]. Further elucidation of the potential mechanism responsible for the observed reduced colonic phagocytic cell infiltration reveals that the induction of bacterial-induced KC expression, one of the major chemoattractants responsible for recruiting neutrophil, is MyD88 dependent (Figure 5) and that helminth co-infection completely abolished such response in MyD88 knockout mice (Figure 5).…”

Section: Discussionsupporting

confidence: 91%

Development of Fatal Intestinal Inflammation in MyD88 Deficient Mice Co-infected with Helminth and Bacterial Enteropathogens

Zhang

et al. 2014

PLoS Negl Trop Dis

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Infections with intestinal helminth and bacterial pathogens, such as enteropathogenic Escherichia coli, continue to be a major global health threat for children. To determine whether and how an intestinal helminth parasite, Heligomosomoides polygyrus, might impact the TLR signaling pathway during the response to a bacterial enteropathogen, MyD88 knockout and wild-type C57BL/6 mice were infected with H. polygyrus, the bacterial enteropathogen Citrobacter rodentium, or both. We found that MyD88 knockout mice co-infected with H. polygyrus and C. rodentium developed more severe intestinal inflammation and elevated mortality compared to the wild-type mice. The enhanced susceptibility to C. rodentium, intestinal injury and mortality of the co-infected MyD88 knockout mice were found to be associated with markedly reduced intestinal phagocyte recruitment, decreased expression of the chemoattractant KC, and a significant increase in bacterial translocation. Moreover, the increase in bacterial infection and disease severity were found to be correlated with a significant downregulation of antimicrobial peptide expression in the intestinal tissue in co-infected MyD88 knockout mice. Our results suggest that the MyD88 signaling pathway plays a critical role for host defense and survival during helminth and enteric bacterial co-infection.

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Section: Discussionsupporting

confidence: 91%

Development of Fatal Intestinal Inflammation in MyD88 Deficient Mice Co-infected with Helminth and Bacterial Enteropathogens

Zhang

et al. 2014

PLoS Negl Trop Dis

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“…The immune-signaling mechanism for the strong cellular response demonstrated that myeloid differentiation primary response protein 88 ( MyD88 )-mediated signaling contributes to proinflammatory cytokine responses [22 ▪▪ ]. These results were consistent with earlier reports which showed that MyD88 −/− mice were highly susceptible to pulmonary challenges with B. mallei and had significantly short survival time, increased bacterial burdens, and severe organ pathology compared with wild-type mice [23]. Recruitment of inflammatory monocytes and Dendritic Cells to the lungs and local production of IL-12, followed by Natural killer cell cell production of IFNγ, are the key cellular responses required for early protection from B. mallei infection.…”

Section: Cytokines and Chemokine Regulating Innate Immunity To B Malsupporting

confidence: 93%

Innate immune response to Burkholderia mallei

Saikh

Mott

2017

Current Opinion in Infectious Diseases

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Purpose of reviewBurkholderia mallei is a facultative intracellular pathogen that causes the highly contagious and often the fatal disease, glanders. With its high rate of infectivity via aerosol and recalcitrance toward antibiotics, this pathogen is considered a potential biological threat agent. This review focuses on the most recent literature highlighting host innate immune response to B. mallei.Recent findingsRecent studies focused on elucidating host innate immune responses to the novel mechanisms and virulence factors employed by B. mallei for survival. Studies suggest that pathogen proteins manipulate various cellular processes, including host ubiquitination pathways, phagosomal escape, and actin–cytoskeleton rearrangement. Immune-signaling molecules such as Toll-like receptors, nucleotode-binding oligomerization domain, myeloid differentiation primary response protein 88, and proinflammatory cytokines such as interferon-gamma and tumor necrosis factor-α, play key roles in the induction of innate immune responses. Modifications in B. mallei lipopolysaccharide, in particular, the lipid A acyl groups, stimulate immune responses via Toll-like receptor4 activation that may contribute to persistent infection.SummaryMortality is high because of septicemia and immune pathogenesis with B. mallei exposure. An effective innate immune response is critical to controlling the acute phase of the infection. Both vaccination and therapeutic approaches are necessary for complete protection against B. mallei.

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“…Thus, in B. pseudomallei infection, TLR2 can be stimulated directly, whereas activation of TLR4 requires the coreceptors CD14 and MD2 (Hii et al, 2008). Mice lacking the TLR2 receptor are actually protected from B. pseudomallei infection, whereas TLR4 defective mice do not exhibit increased susceptibility to either B. mallei or B. pseudomallei infection (Wiersinga et al, 2007b; Goodyear et al, 2012b). Macrophage activation by B. pseudomallei results in production of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6 (West et al, 2008).…”

Section: Host Immune Response To Burkholderia Infectionmentioning

confidence: 99%

“…For example, MyD88 −/− mice infected with either B. pseudomallei or B. mallei were much more susceptible to infection than wild type mice (Wiersinga et al, 2008; Goodyear et al, 2012b). Interestingly, in MyD88 −/− mice infected with B. pseudomallei , there was reduced early pulmonary neutrophil recruitment and a diminished activation of neutrophils compared to wild type mice (Wiersinga et al, 2008).…”

Section: Host Immune Response To Burkholderia Infectionmentioning

confidence: 99%

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Development of Burkholderia mallei and pseudomallei vaccines

Silva¹,

Dow²

2013

Front. Cell. Infect. Microbiol.

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Burkholderia mallei and Burkholderia pseudomallei are Gram-negative bacteria that cause glanders and melioidosis, respectively. Inhalational infection with either organism can result in severe and rapidly fatal pneumonia. Inoculation by the oral and cutaneous routes can also produce infection. Chronic infection may develop after recovery from acute infection with both agents, and control of infection with antibiotics requires prolonged treatment. Symptoms for both meliodosis and glanders are non-specific, making diagnosis difficult. B. pseudomallei can be located in the environment, but in the host, B. mallei and B. psedomallei are intracellular organisms, and infection results in similar immune responses to both agents. Effective early innate immune responses are critical to controlling the early phase of the infection. Innate immune signaling molecules such as TLR, NOD, MyD88, and pro-inflammatory cytokines such as IFN-γ and TNF-α play key roles in regulating control of infection. Neutrophils and monocytes are critical cells in the early infection for both microorganisms. Both monocytes and macrophages are necessary for limiting dissemination of B. pseudomallei. In contrast, the role of adaptive immune responses in controlling Burkholderia infection is less well understood. However, T cell responses are critical for vaccine protection from Burkholderia infection. At present, effective vaccines for prevention of glanders or meliodosis have not been developed, although recently development of Burkholderia vaccines has received renewed attention. This review will summarize current and past approaches to develop B. mallei and B. pseudomalllei vaccines, with emphasis on immune mechanisms of protection and the challenges facing the field. At present, immunization with live attenuated bacteria provides the most effective and durable immunity, and it is important therefore to understand the immune correlates of protection induced by live attenuated vaccines. Subunit vaccines have typically provided less robust immunity, but are safer to administer to a wider variety of people, including immune compromised individuals because they do not reactivate or cause disease. The challenges facing B. mallei and B. pseudomalllei vaccine development include identification of broadly protective antigens, design of efficient vaccine delivery and adjuvant systems, and a better understanding of the correlates of protection from both acute and chronic infection.

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MyD88-Dependent Recruitment of Monocytes and Dendritic Cells Required for Protection from Pulmonary Burkholderia mallei Infection

Cited by 16 publications

References 38 publications

Development of Fatal Intestinal Inflammation in MyD88 Deficient Mice Co-infected with Helminth and Bacterial Enteropathogens

Development of Fatal Intestinal Inflammation in MyD88 Deficient Mice Co-infected with Helminth and Bacterial Enteropathogens

Innate immune response to Burkholderia mallei

Development of Burkholderia mallei and pseudomallei vaccines

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