Persistent bacterial infections: the interface of the pathogen and the host immune system

Monack, Denise M.; Mueller, Anne; Falkow, Stanley

doi:10.1038/nrmicro955

Cited by 475 publications

(401 citation statements)

References 235 publications

Supporting

Mentioning

390

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, loss of sciS attenuates virulence of Typhimurium in mice (Parsons & Heffron, 2005). Controlled growth in host cells has also been linked to chronic infection (Monack et al, 2004;Tierrez & Garcia-del Portillo, 2005). This growth control might explain the longer incubation period of Typhi with respect to Typhimurium.…”

Section: Discussionmentioning

confidence: 99%

A novel PhoP-regulated locus encoding the cytolysin ClyA and the secreted invasin TaiA of Salmonella enterica serovar Typhi is involved in virulence

2009

View full text Add to dashboard Cite

Salmonella enterica serovar Typhi causes a human-restricted systemic infection called typhoid fever. We have identified a Typhi genomic region encoding two ORFs, STY1498 and STY1499, that are expressed during infection of human macrophages and organized in an operon. STY1498 corresponds to clyA, which encodes a pore-forming cytolysin, and STY1499 encodes a 27 kDa protein, without any attributed function, which we have named TaiA (Typhi-associated invasin A). In order to evaluate the roles of these genes in Typhi pathogenesis, isogenic Typhi strains harbouring a non-polar mutation of either clyA or taiA were constructed. In macrophages, taiA was involved in increasing phagocytosis, as taiA deletion reduced bacterial uptake, whereas clyA reduced or controlled bacterial growth, as clyA deletion enhanced Typhi survival within macrophages without affecting cytotoxicity. In epithelial cells, deletion of taiA had no effect on invasion, whereas deletion of clyA enhanced the Typhi invasion rate, and reduced cytotoxicity. Overexpression of taiA in Typhi or in Escherichia coli resulted in a higher invasion rate of epithelial cells. We have demonstrated that TaiA is secreted independently of both the Salmonella pathogenicity island (SPI)-1 and the SPI-2 type three secretion systems. We have shown that this operon is regulated by the virulence-associated regulator PhoP. Moreover, our results revealed that products of this operon might be involved in promoting the use of macrophages as a sheltered reservoir for Typhi and allowing long-term persistence inside the host. INTRODUCTIONThe genus Salmonella is composed of two distinct species, Salmonella bongori and Salmonella enterica. While S. bongori is rarely involved in human infections, S. enterica is a major human pathogen. Out of the 2000 serovars of S. enterica, only a small fraction is associated with human infections (Porwollik et al., 2004). Serovars Typhimurium and Enteritidis cause a localized infection, gastroenteritis, whereas serovar Typhi causes a severe systemic infection called typhoid fever, which kills an estimated 600 000 people annually (Parry et al., 2002). Because Typhi is restricted to humans, Typhimurium has been used for many years to study typhoid fever pathogenesis using a murine infection model in which Typhimurium causes a systemic infection. This model has been crucial in understanding systemic infections by Salmonella.S. enterica and S. bongori possess a type three secretion system (T3SS), encoded by Salmonella pathogenicity island 1 (SPI-1), which mediates invasion of host cells (Galan, 1999;Marcus et al., 2000). Only S. enterica possesses a second T3SS located in SPI-2, which is required for survival inside macrophages and the infection of mammalian hosts . The T3SS injects bacterial proteins directly into the host cell and disturbs normal cell function. Induction of the SPI-1-encoded genes requires high osmolarity and low aeration, conditions present in the small intestine where the SPI-1 T3SS initiates cell invasion (Altier, 2005;Lostroh & Lee,...

show abstract

Section: Discussionmentioning

confidence: 99%

A novel PhoP-regulated locus encoding the cytolysin ClyA and the secreted invasin TaiA of Salmonella enterica serovar Typhi is involved in virulence

2009

View full text Add to dashboard Cite

show abstract

“…[4][5][6][7] Other strains of mice, such as several 129 substrains, are capable of controlling early bacterial replication and survive the infection. 4,8 The wild-derived MOLF/Ei mice are highly susceptible to infection despite the fact that they are capable of controlling bacterial replication in the target organs. 9 An initial genome scan in an F2 cross between the two susceptible strains, C57BL/6J and MOLF/Ei, identified three regions linked to the clinical phenotype: Ity and Ity3 on chromosome 1 and Ity2 on chromosome 11.…”

Section: Introductionmentioning

confidence: 99%

Refinement of the genetics of the host response to Salmonella infection in MOLF/Ei: regulation of type 1 IFN and TRP3 pathways by Ity2

et al. 2011

View full text Add to dashboard Cite

Typhoid fever, which is caused by Salmonella typhi and paratyphi, is a severe systemic disease that remains a major public health issue in several areas of the world. We can model the human disease using mice infected with a related bacterium, Salmonella typhimurium. This model recapitulates several clinical aspects of the human disease and allows for the study of the host response to Salmonella typhimurium infection in vivo. Previous work in our laboratory has identified three Immunity to typhimurium loci (Ity, Ity2 and Ity3) in the wild-derived MOLF/Ei mice, influencing survival after infection with Salmonella typhimurium. The MOLF/Ei alleles at Ity and Ity2 are protective, while the MOLF/Ei allele at Ity3 confers susceptibility. In this paper, we have generated a novel cross combination between the highly susceptible strain, MOLF/Ei, and the resistant strain, 129S6, to better define the genetic architecture of susceptibility to infection in MOLF/Ei. Using this cross, we have replicated the locus on chr 11 (Ity2) and identified a novel locus on chr 13 (Ity13). Using microarrays and transcriptional profiling, we examined the response of uninfected and infected Ity2 congenic mice. These analyses demonstrate a role for both type-1-interferon (IFN) and TRP53 signaling in the pathogenesis of Salmonella infection.

show abstract

“…Mice engineered to express a single TCR V␤5 chain specific for OVA-8p, thereby reducing diversity to that contributed by the TCR␣ chain alone, do not reject allogeneic bone marrow (28). Similarly, subjects with complete DiGeorge syndrome, a disease characterized by thymic aplasia and decreased thymic output of Ͼ50% (29 -32), and AIDS, a disease characterized by a 10-fold decrease in thymic output (33)(34)(35)(36), have striking "distortion" of the T cell repertoire and are highly susceptible to opportunistic infection (30,37). However, diversity of TCR per se has not been directly measured.…”

Section: Functions Of the T Cell Compartmentmentioning

confidence: 99%

Effacing of the T Cell Compartment by Cardiac Transplantation in Infancy

Ogle

West

Driscoll

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

For cardiac transplantation in infants, T cells are depleted and the thymus is removed. These manipulations should cause profound defects in the T cell compartment. To test this concept, 20 subjects who underwent cardiac transplantation in infancy and healthy age-matched subjects were studied. The number of T cells in the blood was nearly normal in all subjects 1–10 years after surgery. However, newly generated T cells were undetectable in 10 recipients and 10-fold less than controls in 10, suggesting absence of thymic function. TCRβ chain diversity, measured by a novel technique, was ∼100-fold lower than controls. T cell function, deduced from levels of human herpesvirus 7 and response to hepatitis B immunization, were notably impaired. Yet cardiac transplant recipients were generally free of opportunistic infections. Our findings demonstrate a novel approach to measuring lymphocyte diversity and suggest that understanding how these subjects resist infection could yield important insights into immune fitness.

show abstract

Persistent bacterial infections: the interface of the pathogen and the host immune system

Cited by 475 publications

References 235 publications

A novel PhoP-regulated locus encoding the cytolysin ClyA and the secreted invasin TaiA of Salmonella enterica serovar Typhi is involved in virulence

A novel PhoP-regulated locus encoding the cytolysin ClyA and the secreted invasin TaiA of Salmonella enterica serovar Typhi is involved in virulence

Refinement of the genetics of the host response to Salmonella infection in MOLF/Ei: regulation of type 1 IFN and TRP3 pathways by Ity2

Effacing of the T Cell Compartment by Cardiac Transplantation in Infancy

Contact Info

Product

Resources

About