ACTIVATION OF NATURAL KILLER T CELLS BY Α-Galactosylceramide MEDIATES CLEARANCE OF BACTERIA IN MURINE URINARY TRACT INFECTION

Minagawa, Shingo; Οhyama, Chikara; Tsuchiya, Norihiko; Kato, Takumi; Habuchi, Tomonori

doi:10.1097/01.ju.0000158122.16046.68

Cited by 24 publications

(13 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…J H D mice, lacking both B-1 and B-2 cells (43,212), infected and monitored over a 14-day time period exhibited no significant increase in incidence or severity of cystitis (130). On a final note regarding ILLs, administration of ␣-galactosylceramide (␣-GalCer), a ligand for CD1d-restricted NKT cells, alleviates renal UPEC infection (168). Consistent with this, we have observed a resident population of NK1.…”

Section: Special Operations: Ills In the Innate Immune Response To Upsupporting

confidence: 67%

Waging War against UropathogenicEscherichia coli: Winning Back the Urinary Tract

2010

View full text Add to dashboard Cite

Urinary tract infection (UTI) caused by uropathogenic Escherichia coli (UPEC) is a substantial economic and societal burden-a formidable public health issue. Symptomatic UTI causes significant discomfort in infected patients, results in lost productivity, predisposes individuals to more serious infections, and usually necessitates antibiotic therapy. There is no licensed vaccine available for prevention of UTI in humans in the United States, likely due to the challenge of targeting a relatively heterogeneous group of pathogenic strains in a unique physiological niche. Despite significant advances in the understanding of UPEC biology, mechanistic details regarding the host response to UTI and full comprehension of genetic loci that influence susceptibility require additional work. Currently, there is an appreciation for the role of classic innate immune responses-from pattern receptor recognition to recruitment of phagocytic cells-that occur during UPEC-mediated UTI. There is, however, a clear disconnect regarding how factors involved in the innate immune response to UPEC stimulate acquired immunity that facilitates enhanced clearance upon reinfection. Unraveling the molecular details of this process is vital in the development of a successful vaccine for prevention of human UTI. Here, we survey the current understanding of host responses to UPEC-mediated UTI with an eye on molecular and cellular factors whose activity may be harnessed by a vaccine that stimulates lasting and sterilizing immunity. MISSION: ERADICATE UPEC-MEDIATED UTIUrinary tract infection (UTI) is one of the most common infections in humans. Bacteria present in fecal matter inoculate the periurethral area, then the bladder (124, 176, 291), causing symptoms clinically termed cystitis. Left untreated, bacteria ascend the ureters to the kidney and establish a secondary infection, acute pyelonephritis. At this juncture, there is risk of permanent renal scarring, and bacteria can access the bloodstream (282). It is estimated that 40% of women and 12% of men will experience a symptomatic UTI, with incidences peaking in their early 20s or after age 85, respectively (75, 185). Approximately 25% of these women will experience recurrence within 6 to 12 months (75, 185). Uropathogenic Escherichia coli (UPEC) is the most common etiological agent responsible for uncomplicated UTI (93, 94,282). Uropathogenic strains are classified as extraintestinal pathogenic E. coli, a broad grouping of E. coli that cause diseases other than gastroenteritis and typically lack a type III secretion system (171,220,221,283,284). Nonetheless, UPEC strains express an assortment of virulence and fitness factors that aid in successful colonization of the mammalian urinary tract (126,136). In the United States alone, the estimated annual societal cost of UTI is more than 3 billion dollars (159).Despite a relatively in-depth knowledge base for UPEC physiology and virulence mechanisms (reviewed in references 54, 126, 136, and 284), no licensed vaccine to prevent UTI exists in the Un...

show abstract

Section: Special Operations: Ills In the Innate Immune Response To Upsupporting

confidence: 67%

Waging War against UropathogenicEscherichia coli: Winning Back the Urinary Tract

2010

View full text Add to dashboard Cite

show abstract

“…A significant proportion of hospital cases of sepsis is due to Gram-positive cocci, which induce a different inflammatory response from that of Gram-negative bacteria (25). The function of NKT cells in various milder infections is dependent on the type of infecting agent; thus, NKT cells play a beneficial role in some infections (26,27) and are detrimental in others (11). Therefore, observations from Gram-negative sepsis models cannot be extrapolated to S. aureus sepsis.…”

mentioning

confidence: 91%

Sulfatide Attenuates Experimental Staphylococcus aureus Sepsis through a CD1d-Dependent Pathway

et al. 2013

View full text Add to dashboard Cite

Natural killer T (NKT) lymphocytes are implicated in the early response to microbial infection. Further, sulfatide, a myelin selfglycosphingolipid, activates a type II NKT cell subset and can modulate disease in murine models. We examined the role of NKT cells and the effect of sulfatide treatment in a murine model of Staphylococcus aureus sepsis. The lack of CD1d-restricted NKT cells did not alter survival after a lethal inoculum of S. aureus. In contrast, sulfatide treatment significantly improved the survival rate of mice with S. aureus sepsis, accompanied by decreased levels of tumor necrosis factor alpha and interleukin-6 in the blood. The protective effect of sulfatide treatment depended on CD1d but not on type I NKT cells, suggesting that activation of type II NKT cells by sulfatide has beneficial effects on the outcome of S. aureus sepsis in this model.

show abstract

“…It was found that the C-glycoside induced more of a Th1 (i.e., IFN-␥) response, was longer lasting, and was actually a better adjuvant than the parental compound itself in murine models of malaria and metastatic melanoma (53)(54)(55)(56)(57). Furthermore, ␣-GalCer administration has been shown to be mostly protective activity against viruses (58 -61), bacteria (62)(63)(64)(65)(66)(67), and other pathogens (68,69). In Trypanosoma cruzi, although GPIs and other lipids from this genus can bind to CD1d, those ligands do not stimulate NKT cells (70).…”

Section: ␣-Galactosylceramide (␣-Galcer) and ␣-Galcer Analogsmentioning

confidence: 99%

CD1d Ligands: The Good, the Bad, and the Ugly

Brutkiewicz

2006

The Journal of Immunology

161

132

View full text Add to dashboard Cite

The MHC class I-like CD1d glycoprotein is a member of the CD1 family of Ag-presenting molecules and is responsible for the selection of NKT cells. A number of ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells have been identified. These include glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules. The presentation of many of these molecules can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer or can be deleterious. This review will highlight these ligands in a discussion of their potential use against (and role in the pathogenesis of) these diseases.

show abstract

ACTIVATION OF NATURAL KILLER T CELLS BY Α-Galactosylceramide MEDIATES CLEARANCE OF BACTERIA IN MURINE URINARY TRACT INFECTION

Abstract: These findings suggest a significant role for alpha-GalCer in regulating antibacterial functions by activating natural killer T cells in the murine UTI model.

Cited by 24 publications

References 20 publications

Waging War against UropathogenicEscherichia coli: Winning Back the Urinary Tract

Waging War against UropathogenicEscherichia coli: Winning Back the Urinary Tract

Sulfatide Attenuates Experimental Staphylococcus aureus Sepsis through a CD1d-Dependent Pathway

CD1d Ligands: The Good, the Bad, and the Ugly

Contact Info

Product

Resources

About