Differential responses of chicken monocyte-derived dendritic cells infected with Salmonella Gallinarum and Salmonella Typhimurium

AbstractSalmonella enterica serovar Gallinarum is a host-restricted bacterial pathogen that causes a serious systemic disease exclusively in birds of all ages. Salmonella enterica serovar Typhimurium is a host-generalist serovar. Dendritic cells (DCs) are key antigen-presenting cells that play an important part in Salmonella host-restriction. We evaluated the differential response of chicken blood monocyte-derived dendritic cells (chMoDCs) exposed to S. Gallinarum or S. Typhimurium. S. Typhimurium was found to be more invasive while S. Gallinarum was more cytotoxic at the early phase of infection and later showed higher resistance against chMoDCs killing. S. Typhimurium promoted relatively higher upregulation of costimulatory and other immune function genes on chMoDCs in comparison to S. Gallinarum during early phase of infection (6 h) as analyzed by real-time PCR. Both Salmonella serovars strongly upregulated the proinflammatory transcripts, however, quantum was relatively narrower with S. Gallinarum. S. Typhimurium-infected chMoDCs promoted relatively higher proliferation of naïve T-cells in comparison to S. Gallinarum as assessed by mixed lymphocyte reaction. Our findings indicated that host restriction of S. Gallinarum to chicken is linked with its profound ability to interfere the DCs function. Present findings provide a valuable roadmap for future work aimed at improved vaccine strategies against this pathogen.

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Role of Nod1 in Mucosal Dendritic Cells during Salmonella Pathogenicity Island 1-Independent Salmonella enterica Serovar Typhimurium Infection

Infection and Immunity ◽

10.1128/iai.00519-09 ◽

2009 ◽

Vol 77 (10) ◽

pp. 4480-4486 ◽

Cited By ~ 34

Author(s):

Lionel Le Bourhis ◽

Joao Gamelas Magalhaes ◽

Thirumahal Selvanantham ◽

Leonardo H. Travassos ◽

Kaoru Geddes ◽

...

Keyword(s):

Dendritic Cells ◽

Lamina Propria ◽

Salmonella Enterica ◽

Severe Disease ◽

Bacterial Pathogen ◽

Critical Function ◽

Intestinal Lamina Propria ◽

Serovar Typhimurium

ABSTRACT Recent advances in immunology have highlighted the critical function of pattern-recognition molecules (PRMs) in generating the innate immune response to effectively target pathogens. Nod1 and Nod2 are intracellular PRMs that detect peptidoglycan motifs from the cell walls of bacteria once they gain access to the cytosol. Salmonella enterica serovar Typhimurium is an enteric intracellular pathogen that causes a severe disease in the mouse model. This pathogen resides within vacuoles inside the cell, but the question of whether cytosolic PRMs such as Nod1 and Nod2 could have an impact on the course of S. Typhimurium infection in vivo has not been addressed. Here, we show that deficiency in the PRM Nod1, but not Nod2, resulted in increased susceptibility toward a mutant strain of S. Typhimurium that targets directly lamina propria dendritic cells (DCs) for its entry into the host. Using this bacterium and bone marrow chimeras, we uncovered a surprising role for Nod1 in myeloid cells controlling bacterial infection at the level of the intestinal lamina propria. Indeed, DCs deficient for Nod1 exhibited impaired clearance of the bacteria, both in vitro and in vivo, leading to increased organ colonization and decreased host survival after oral infection. Taken together, these findings demonstrate a key role for Nod1 in the host response to an enteric bacterial pathogen through the modulation of intestinal lamina propria DCs.

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Salmonella enterica Serovar Typhimurium-Induced Maturation of Bone Marrow-Derived Dendritic Cells

Infection and Immunity ◽

10.1128/.68.11.6311-6320.2000 ◽

2000 ◽

Vol 68 (11) ◽

pp. 6311-6320

Author(s):

Mattias Svensson ◽

Cecilia Johansson ◽

Mary Jo Wick

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Salmonella Enterica ◽

Salmonella Enterica Serovar Typhimurium ◽

Serovar Typhimurium

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QseC Mediates Salmonella enterica Serovar Typhimurium Virulence In Vitro and In Vivo

Infection and Immunity ◽

10.1128/iai.01038-09 ◽

2009 ◽

Vol 78 (3) ◽

pp. 914-926 ◽

Cited By ~ 102

Author(s):

Cristiano G. Moreira ◽

David Weinshenker ◽

Vanessa Sperandio

Keyword(s):

Epithelial Cells ◽

Salmonella Enterica ◽

Systemic Disease ◽

Systemic Infection ◽

Flagellar Motility ◽

Signaling System ◽

Interkingdom Signaling ◽

Serovar Typhimurium

ABSTRACT The autoinducer-3 (AI-3)/epinephrine (Epi)/norepinephrine (NE) interkingdom signaling system mediates chemical communication between bacteria and their mammalian hosts. The three signals are sensed by the QseC histidine kinase (HK) sensor. Salmonella enterica serovar Typhimurium is a pathogen that uses HKs to sense its environment and regulate virulence. Salmonella serovar Typhimurium invades epithelial cells and survives within macrophages. Invasion of epithelial cells is mediated by the type III secretion system (T3SS) encoded in Salmonella pathogenicity island 1 (SPI-1), while macrophage survival and systemic disease are mediated by the T3SS encoded in SPI-2. Here we show that QseC plays an important role in Salmonella serovar Typhimurium pathogenicity. A qseC mutant was impaired in flagellar motility, in invasion of epithelial cells, and in survival within macrophages and was attenuated for systemic infection in 129x1/SvJ mice. QseC acts globally, regulating expression of genes within SPI-1 and SPI-2 in vitro and in vivo (during infection of mice). Additionally, dopamine β-hydroxylase knockout (Dbh − / −) mice that do not produce Epi or NE showed different susceptibility to Salmonella serovar Typhimurium infection than wild-type mice. These data suggest that the AI-3/Epi/NE signaling system is a key factor during Salmonella serovar Typhimurium pathogenesis in vitro and in vivo. Elucidation of the role of this interkingdom signaling system in Salmonella serovar Typhimurium should contribute to a better understanding of the complex interplay between the pathogen and the host during infection.

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Salmonella enterica serovar Typhimurium interaction with dendritic cells: impact of the sifA gene

Cellular Microbiology ◽

10.1111/j.1462-5822.2004.00419.x ◽

2004 ◽

Vol 6 (11) ◽

pp. 1071-1084 ◽

Cited By ~ 21

Author(s):

Liljana Petrovska ◽

Richard J. Aspinall ◽

Li Barber ◽

Simon Clare ◽

Cameron P. Simmons ◽

...

Keyword(s):

Dendritic Cells ◽

Salmonella Enterica ◽

Salmonella Enterica Serovar Typhimurium ◽

Serovar Typhimurium

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Activation of murine dendritic cells and macrophages induced by Salmonella enterica serovar Typhimurium

Immunology ◽

10.1111/j.1365-2567.2005.02180.x ◽

2005 ◽

Vol 115 (4) ◽

pp. 462-472 ◽

Cited By ~ 26

Author(s):

Ruwani Sagarika Kalupahana ◽

Pietro Mastroeni ◽

Duncan Maskell ◽

Barbara Ann Blacklaws

Keyword(s):

Dendritic Cells ◽

Salmonella Enterica ◽

Salmonella Enterica Serovar Typhimurium ◽

Serovar Typhimurium

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RIG-I Detects mRNA of Intracellular Salmonella enterica Serovar Typhimurium during Bacterial Infection

mBio ◽

10.1128/mbio.01006-14 ◽

2014 ◽

Vol 5 (2) ◽

Cited By ~ 29

Author(s):

Mirco Schmolke ◽

Jenish R. Patel ◽

Elisa de Castro ◽

Maria T. Sánchez-Aparicio ◽

Melissa B. Uccellini ◽

...

Keyword(s):

Salmonella Enterica ◽

Bacterial Pathogen ◽

Host Immune System ◽

Sequencing Analysis ◽

Phagocytic Cells ◽

Content Type ◽

Oral Transmission ◽

Molecular Pattern ◽

Serovar Typhimurium ◽

Next Generation Sequencing Analysis

ABSTRACT The cytoplasmic helicase RIG-I is an established sensor for viral 5′-triphosphorylated RNA species. Recently, RIG-I was also implicated in the detection of intracellular bacteria. However, little is known about the host cell specificity of this process and the bacterial pathogen-associated molecular pattern (PAMP) that activates RIG-I. Here we show that RNA of Salmonella enterica serovar Typhimurium activates production of beta interferon in a RIG-I-dependent fashion only in nonphagocytic cells. In phagocytic cells, RIG-I is obsolete for detection of Salmonella infection. We further demonstrate that Salmonella mRNA reaches the cytoplasm during infection and is thus accessible for RIG-I. The results from next-generation sequencing analysis of RIG-I-associated RNA suggest that coding bacterial mRNAs represent the activating PAMP. IMPORTANCE S. Typhimurium is a major food-borne pathogen. After fecal-oral transmission, it can infect epithelial cells in the gut as well as immune cells (mainly macrophages, dendritic cells, and M cells). The innate host immune system relies on a growing number of sensors that detect pathogen-associated molecular patterns (PAMPs) to launch a first broad-spectrum response to invading pathogens. Successful detection of a given pathogen depends on colocalization of host sensors and PAMPs as well as potential countermeasures of the pathogen during infection. RIG-I-like helicases were mainly associated with detection of RNA viruses. Our work shows that S. Typhimurium is detected by RIG-I during infection specifically in nonimmune cells.

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Abelson Tyrosine Kinase Facilitates Salmonella enterica Serovar Typhimurium Entry into Epithelial Cells

Infection and Immunity ◽

10.1128/iai.00639-08 ◽

2008 ◽

Vol 77 (1) ◽

pp. 60-69 ◽

Cited By ~ 23

Author(s):

Kim Thien Ly ◽

James E. Casanova

Keyword(s):

Tyrosine Kinase ◽

Salmonella Enterica ◽

Salmonella Enterica Serovar Typhimurium ◽

Bacterial Pathogen ◽

Adaptor Protein ◽

Effector Proteins ◽

Interacting Protein ◽

Abelson Tyrosine Kinase ◽

System A ◽

Serovar Typhimurium

ABSTRACT The intracellular gram-negative bacterial pathogen Salmonella enterica serovar Typhimurium gains entry into nonphagocytic cells by manipulating the assembly of the host actin cytoskeleton. S. enterica serovar Typhimurium entry requires a functional type III secretion system, a conduit through which bacterial effector proteins are directly translocated into the host cytosol. We and others have previously reported the enhancement of tyrosine kinase activities during Salmonella serovar Typhimurium infection; however, neither specific kinases nor their targets have been well characterized. In this study, we investigated the roles of the cellular Abelson tyrosine kinase (c-Abl) and the related protein Arg in the context of serovar Typhimurium infection. We found that bacterial internalization was inhibited by more than 70% in cells lacking both c-Abl and Arg and that treatment of wild-type cells with a pharmaceutical inhibitor of the c-Abl kinase, STI571 (imatinib), reduced serovar Typhimurium invasion efficiency to a similar extent. Bacterial infection led to enhanced phosphorylation of two previously identified c-Abl substrates, the adaptor protein CT10 regulator of kinase (CrkII) and the Abelson-interacting protein Abi1, a component of the WAVE2 complex. Furthermore, overexpression of the nonphosphorylatable form of CrkII resulted in decreased invasion. Taken together, these findings indicate that c-Abl is activated during S. enterica serovar Typhimurium infection and that its phosphorylation of multiple downstream targets is functionally important in bacterial internalization.

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Gamma Interferon-Independent Effects of Interleukin-12 on Immunity to Salmonella enterica Serovar Typhimurium

Infection and Immunity ◽

10.1128/iai.00971-07 ◽

2007 ◽

Vol 75 (12) ◽

pp. 5753-5762 ◽

Cited By ~ 9

Author(s):

Jason D. Price ◽

Kim R. Simpfendorfer ◽

Radhakrishnam R. Mantena ◽

James Holden ◽

William R. Heath ◽

...

Keyword(s):

T Cells ◽

Salmonella Enterica ◽

Bacterial Load ◽

Bacterial Pathogen ◽

Cell Receptor ◽

Gamma Interferon ◽

Interleukin 12 ◽

Mesenteric Lymph Nodes ◽

Serovar Typhimurium ◽

Ifn Γ

ABSTRACTInterleukin-12 (IL-12) and IL-18 are both central to the induction of gamma interferon (IFN-γ), and various roles for IL-12 and IL-18 in control of intracellular microbial infections have been demonstrated. We used IL-12p40−/−and IL-18−/−mice to further investigate the role of IL-12 and IL-18 in control ofSalmonella entericaserovar Typhimurium. While C57BL/6 and IL-18−/−mice were able to resolve attenuatedS. entericaserovar Typhimurium infections, the IL-12p40−/−mice succumbed to a high bacterial burden after 60 days. Using ovalbumin (OVA)-specific T-cell receptor transgenic T cells (OT-II cells), we demonstrated that following oral infection with recombinantS. entericaserovar Typhimurium expressing OVA, the OT-II cells proliferated in the mesenteric lymph nodes of C57BL/6 and IL-18−/−mice but not in IL-12p40−/−mice. In addition, we demonstrated by flow cytometry that equivalent or increased numbers of T cells produced IFN-γ in IL-12p40−/−mice compared with the numbers of T cells that produced IFN-γ in C57BL/6 and IL-18−/−mice. Finally, we demonstrated that removal of macrophages fromS. entericaserovar Typhimurium-infected C57BL/6 and IL-12p40−/−mice did not affect the bacterial load, suggesting that impaired control ofS. entericaserovar Typhimurium infection in the absence of IL-12p40 is not due to reduced macrophage bactericidal activities, while IL-18−/−mice did rely on the presence of macrophages for control of the infection. Our results suggest that IL-12p40, but not IL-18, is critical to resolution of infections with attenuatedS. entericaserovar Typhimurium and that especially the effects of IL-12p40 on proliferative responses of CD4+T cells, but not the ability of these cells to produce IFN-γ, are important in the resolution of infection by this intracellular bacterial pathogen.

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