Neutrophil depletion increases susceptibility to systemic and vaginal candidiasis in mice, and reveals differences between brain and kidney in mechanisms of host resistance

Fulurija, Alma; Ashman, R. B.; Papadimitriou, John

doi:10.1099/13500872-142-12-3487

Cited by 92 publications

(87 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, neutrophil depletion causes an acute increase in the susceptibility of the heart and kidney, whereas the brain is only slightly affected [37]. Thus, antibody may, depending on its specificity and isotype, act to protect different organsd in BALB/c mice, the brain but not the kidney, and the kidney but not the brain after immunisation with SC5314.…”

Section: Discussionmentioning

confidence: 99%

Isolates of Candida albicans that differ in virulence for mice elicit strain-specific antibody-mediated protective responses

Farah

Ashman

2006

Microbes and Infection

View full text Add to dashboard Cite

Three distinct isolates of Candida albicans were used to establish systemic and oral infections in inbred mice that are genetically resistant or susceptible to tissue damage. Patterns of infection differed significantly between both yeasts and mouse strains. Systemic infection conferred significant protection against re-challenge with the homologous, but not the heterologous yeast; however, the protective effect was more evident in the tissue-susceptible CBA/CaH mice than in the resistant BALB/c strain. In contrast, oral infection induced protection against both homologous and heterologous oral challenge, although this was significant only in the CBA/CaH mice. CBA/CaH mice produced antibodies of both IgG1 and IgG2a subclasses, whereas BALB/c mice produced predominantly IgG1. Western blotting demonstrated considerable differences between epitopes recognised by serum antibodies from mice of both strains after immunisation with each of the three yeasts. Thus, different strains of yeast show considerable specificity in antibody responses elicited by either systemic or oral infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Isolates of Candida albicans that differ in virulence for mice elicit strain-specific antibody-mediated protective responses

Farah

Ashman

2006

Microbes and Infection

View full text Add to dashboard Cite

show abstract

“…This suggests that host factors play a more important role in determining quantitative tissue burdens than any virulence factors in the fungus, once infection has been established in tissues by administration of a suitably large inoculum. Several prior studies have shown that, in a murine host, the genetic background of the mouse strain determines not just overall susceptibility to intravenous C. albicans challenge, but also the susceptibility of individual host tissues to infection by circulating fungus cells (Ashman & Bolitho, 1993 ;Ashman et al, 1991Ashman et al, , 1996Ashman et al, , 1997Fulurija et al, 1996). The mouse gene products that regulate the susceptibility of individual tissues to the fungus have been designated Carg1p and Carg2p (Ashman et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…The criterion for virulence is usually measurement of survival times of intravenously infected mice Bulawa et al, 1995 ;Buurman et al, 1998 ;Calera et al, 1999Calera et al, , 2000Csank et al, 1998 ;De Bernardis et al, 1998 ;DiezOrejas et al, 1997 ;Gale et al, 1998 ;Ghannoum, 1998 ;Ghannoum et al, 1995 ;Hube et al, 1997 ;Jiang et al, 1997 ;Kvaal et al, 1997 ;Lay et al, 1998 ;Leberer et al, 1997 ;Leidich et al, 1999 ;Lo et al, 1997 ;Mio et al, 1996 ;Monge et al, 1999 ;Sanglard et al, 1997 ;Sarthy et al, 1997 ;Timpel et al, 1998 ;Wysong et al, 1998 ;Yaar et al, 1997 ;Yamada-Okabe et al, 1999 ;Zhao et al, 1997). This approach determines a strain's gross lethality but takes no account of likely differences in challenge susceptibility of individual mouse strains, where im- mune responses to C. albicans depend on the genetic background of the animal challenged (Ashman & Bolitho, 1993 ;Ashman et al, 1991Ashman et al, , 1996Ashman et al, , 1997Fulurija et al, 1996). Nor does it distinguish between virulence differences that relate to host-fungus interactions occurring immediately after challenge, when the majority of injected C. albicans are cleared from the circulation within minutes (Baine et al, 1974 ;Iannini et al, 1977 ;Jeunet et al, 1970 ;Rink et al, 1981 ;Sawyer et al, 1976)…”

Section: Introductionmentioning

confidence: 99%

Survival in experimental Candida albicans infections depends on inoculum growth conditions as well as animal host

2000

View full text Add to dashboard Cite

Evidence is presented that the growth medium used to prepare a Candida albicans challenge inoculum is a significant factor determining the ability of a fungus strain to gain an initial invasive hold immediately after injection into an animal host, and thus determining gross strain lethality. Three C. albicans strains, one known to be attenuated in virulence, were grown in two broth media and injected intravenously at different doses into female NMRI mice and male albino guinea pigs. For each fungus strain and challenge dose, survival was longer from inocula grown in a diluted, buffered peptone-based broth than from inocula grown in Sabouraud glucose broth. When animals were challenged intravenously with yeast doses adjusted to give the same mean survival time regardless of strain or growth medium, the progression of fungus tissue burdens (c.f.u. g N1 ) in kidneys, lungs, liver, spleen and brain samples was broadly similar for all three C. albicans strains but differed between the two animal hosts. The morphological form of C. albicans recovered from infected tissues differed at the level of both the fungus strain and the host tissue. Use of survival-standardized inocula provides a means of distinguishing differences in progression of experimental disseminated Candida infections that are related to the infecting strain from those related to the animal host.

show abstract

“…Three months after transplant, WT and KO mouse chimeras appeared healthy, with peripheral leukocytes confirmed to be more than 93% of donor origin (CD45.2) and without significant differences in the CD11b + Gr1 + neutrophil population (data not shown). However, when recipient mice were challenged with non-pathogenic Candida albicans extracts, which are known to trigger neutrophil-dependent inflammatory responses [43], KO but not WT mouse chimera experienced massive alveolar MCA771GA + /neutrophil infiltration ( Figure 6A and 6B) and died within 12 h after immunization. In situ detection of enhanced CRAMP and S100A9 production ( Figure 6C and 6D) in AKNA KO but not in WT mouse chimeras was indicative of rapid neutrophil mobilization and recruitment to the alveolar compartment.…”

Section: Bone Marrow Transplants and Neutrophil-specific Alveolar Damagementioning

confidence: 99%

Coordinate activation of inflammatory gene networks, alveolar destruction and neonatal death in AKNA deficient mice

Ortiz‐Quintero

Rangel

et al. 2011

Cell Res

View full text Add to dashboard Cite

Gene expression can be regulated by chromatin modifiers, transcription factors and proteins that modulate DNA architecture. Among the latter, AT-hook transcription factors have emerged as multifaceted regulators that can activate or repress broad A/T-rich gene networks. Thus, alterations of AT-hook genes could affect the transcription of multiple genes causing global cell dysfunction. Here we report that targeted deletions of mouse AKNA, a hypothetical AT-hook-like transcription factor, sensitize mice to pathogen-induced inflammation and cause sudden neonatal death. Compared with wild-type littermates, AKNA KO mice appeared weak, failed to thrive and most died by postnatal day 10. Systemic inflammation, predominantly in the lungs, was accompanied by enhanced leukocyte infiltration and alveolar destruction. Cytologic, immunohistochemical and molecular analyses revealed CD11b + Gr1 + neutrophils as major tissue infiltrators, neutrophilic granule protein, cathelin-related antimicrobial peptide and S100A8/9 as neutrophil-specific chemoattracting factors, interleukin-1β and interferon-γ as proinflammatory mediators, and matrix metalloprotease 9 as a plausible proteolytic trigger of alveolar damage. AKNA KO bone marrow transplants in wildtype recipients reproduced the severe pathogen-induced reactions and confirmed the involvement of neutrophils in acute inflammation. Moreover, promoter/reporter experiments showed that AKNA could act as a gene repressor. Our results support the concept of coordinated pathway-specific gene regulation functions modulating the intensity of inflammatory responses, reveal neutrophils as prominent mediators of acute inflammation and suggest mechanisms underlying the triggering of acute and potentially fatal immune reactions.

show abstract

Neutrophil depletion increases susceptibility to systemic and vaginal candidiasis in mice, and reveals differences between brain and kidney in mechanisms of host resistance

Cited by 92 publications

References 32 publications

Isolates of Candida albicans that differ in virulence for mice elicit strain-specific antibody-mediated protective responses

Isolates of Candida albicans that differ in virulence for mice elicit strain-specific antibody-mediated protective responses

Survival in experimental Candida albicans infections depends on inoculum growth conditions as well as animal host

Coordinate activation of inflammatory gene networks, alveolar destruction and neonatal death in AKNA deficient mice

Contact Info

Product

Resources

About