The availability of purines influences both the number of parasites and the splenocyte levels of purine-metabolizing enzymes in trypanosome-infected mice

Albright, Julia W.; Albright, Joseph F.

doi:10.1128/iai.56.4.831-835.1988

Cited by 6 publications

(2 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It seems probable that the magnitude of infection (i.e., the total T. musculi per mouse) is controlled by the capability of the generative subpopulation and that such capability is a reflection of the availability of essential nutrients (possibly growth-promoting factors) provided by the host. Strong candidates for limiting nutrients are the available purines and pyrimidines which the trypanosomes appear unable to synthesize but obtain from the host (3,14). Depletion of purines and pyrimidines from the blood, but a continuous although limited supply in the PS, could explain the apparent shift in generative activity from the blood to the PS.…”

Section: Discussionmentioning

confidence: 99%

Immune and nonimmune regulation of the population of Trypanosoma musculi in infected host mice

Albright

Pierantoni

1990

Infect Immun

Self Cite

View full text Add to dashboard Cite

A clear understanding of the population dynamics of trypanosome infections is lacking. In the case of murine Trypanosoma musculi infections, there are no answers to questions concerning (i) the nature of the prolonged plateau phase during which the number of parasites present in the host remains nearly constant (is it a static or dynamic steady state?); (ii) the origin of new parasites, if the plateau is a dynamic steady state, given the relatively early disappearance of generative forms from the bloodstream; and (iii) the role, if any, of a putative ablastin (reproduction-restricting antibody) in regulating the population dynamics of T. musculi infections. We describe here the results of studies of the number and distribution of mature and reproductive forms (RF) in the blood and peritoneal space of both immunocompetent and cyclophosphamide-treated mice throughout the course of infection. While the RF disappeared from the blood within a few days after parasite inoculation, a high fraction (20 to 30%) of the parasites in the peritoneal space were RF throughout the course of infection and, thus, represented a source of new parasites. If an ablastin is responsible for inhibiting RF in the blood, it appeared to have no effect on RF in the peritoneal space. The results of this investigation support the conclusion that the control of the dynamics of T. musculi infections is largely nonimmunological (until cure of the infection) and probably is exercised by the supply of nutrients and reproduction-inhibiting (nonimmunological) and maturation-promoting factors that affect the generative fraction of the population.

show abstract

Section: Discussionmentioning

confidence: 99%

Immune and nonimmune regulation of the population of Trypanosoma musculi in infected host mice

Albright

Pierantoni

1990

Infect Immun

Self Cite

View full text Add to dashboard Cite

show abstract

“…Purine salvage has been seen as an obvious target for drug discovery against the trypanosomatids ever since the lack of de novo purine biosynthesis was discovered in the 1970–1980s (Marr et al 1978 , Gutteridge and Gaborak 1979 , Fish et al 1982 ). Subsequently, it has been shown that the plasma level of salvageable purines is a limiting factor for the proliferation of salivarian trypanosomes as shown in T. musculi -infected mice (Albright and Albright 1988 ). However, the major purine sources in human plasma available for salvage are a matter of controversy because the analyses are very sensitive to how the samples are handled.…”

Section: Purine Sources and Inhibitors Of Purine Salvagementioning

confidence: 99%

Targeting the nucleotide metabolism of Trypanosoma brucei and other trypanosomatids

Hofer

2023

FEMS Microbiology Reviews

View full text Add to dashboard Cite

African sleeping sickness, Chagas disease, and leishmaniasis are life-threatening diseases that together affect millions of people around the world and are caused by different members of the protozoan family Trypanosomatidae. The most-studied member of the family is Trypanosoma brucei, which is spread by tsetse flies and causes African sleeping sickness. Nucleotide metabolism in T. brucei and other trypanosomatids is significantly different from that of mammals and was recognized as a target for chemotherapy already in the 1970s–1980 s. A more thorough investigation of the nucleotide metabolism in recent years has paved the way for identifying nucleoside analogues that can cure T. brucei brain infections in animal models. Specific features of T. brucei nucleotide metabolism include the lack of de novo purine biosynthesis, the presence of very efficient purine transporters, the lack of salvage pathways for CTP synthesis, unique enzyme localizations, and a recently discovered novel pathway for dTTP synthesis. This review describes the nucleotide metabolism of T. brucei, highlights differences and similarities to other trypanosomatids, and discusses how to exploit the parasite-specific features for drug development.

show abstract

Antibody-facilitated macrophage killing of Trypanosoma musculi is an extracellular process as studied in several variations Of an in vitro analytical system

Albright

Stewart

Latham

et al. 1994

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Antibody-facilitated macrophage (MP) destruction of Trypanosoma musculi involves ingestion and intracellular degradation of the parasites. It is likely, however, as we show here, that death of the trypanosomes is extracellular and it is the corpses that are ingested by MPs. We have utilized both peritoneal MPs and a cloned line (WLG 5) of mouse MPs to analyze the killing of T. musculi. Both types of MP were more effective when activated by interferon-gamma (IFN-gamma) rather than lipopolysaccharide (LPS). When activated by both, LPS diminished the killing activity stimulated by IFN-gamma, perhaps by changing the spectrum of lysins/toxins released by the MPs. Nitric oxide (NO) was found to be toxic for T. musculi and to be responsible, in part, for MP killing of the parasites. Although antibody and complement in concert caused lysis of T musculi, complement was not required for MP killing of the parasites. In the course of this investigation, we developed an in vitro system, involving line 5 MPs and plasma from infected mice containing resident parasites, that should prove satisfactory for detailed analyses of the mechanisms of the antibody-dependent, cell-mediated cure of T. musculi infection.

show abstract

The availability of purines influences both the number of parasites and the splenocyte levels of purine-metabolizing enzymes in trypanosome-infected mice

Cited by 6 publications

References 25 publications

Immune and nonimmune regulation of the population of Trypanosoma musculi in infected host mice

Immune and nonimmune regulation of the population of Trypanosoma musculi in infected host mice

Targeting the nucleotide metabolism of Trypanosoma brucei and other trypanosomatids

Antibody-facilitated macrophage killing of Trypanosoma musculi is an extracellular process as studied in several variations Of an in vitro analytical system

Contact Info

Product

Resources

About