Use of cortisone derivatives to inhibit resistance to Nippostrongylus brasiliensis and to study the fate of parasites in resistant hosts

Parasitology ◽  
1965 ◽  
Vol 55 (4) ◽  
pp. 723-730 ◽  
Author(s):  
Bridget M. Ogilvie

Acquired resistance to some nematode parasites can be suppressed by daily administration of cortisone acetate to the host. Cortisone treatment completely suppressed previously acquired resistance of mice to Trichinella spiralis (Coker, 1956) and suppressed, at least partially, the acquisition of resistance to T. spiralis by rats during initial infection (Markell & Lewis, 1957).A previous report (Weinstein, 1955) suggested cortisone acetate treatment was less effective in the suppression of acquired resistance of rats to Nippostrongylus brasiliensis. Weinstein showed that daily treatment with 2 mg cortisone acetate throughout five immunizing infections and continued during the challenge infection increased the number of worms in the intestine and had a marked effect on the cellular response in the skin and lungs. However, there was no significant effect when daily cortisone treatment commenced only on the fifth day before the challenge infection. This result suggested that acquisition of immunity to N. brasiliensis was partially overcome by cortisone treatment, but the same level of drug treatment had no effect on immunity already acquired.In the experiments reported here, previously acquired resistance to N. brasiliensis was suppressed completely and the initiation of immunity stopped, either completely or at a very early stage, by treatment with the cortisone derivatives prednisolone or betamethasone. The complete suspension of all manifestations of acquired resistance obtained by treatment with these drugs was used to investigate the fate of larvae migrating in an immune host.The rats and strain of parasite, and the methods of handling them, have been described previously (Ogilvie, 1965).

Parasitology ◽  
1965 ◽  
Vol 55 (2) ◽  
pp. 325-335 ◽  
Author(s):  
Bridget M. Ogilvie

Immunity to N. brasiliensis in rats is stimulated primarily by the adult worms. An initial infection consisting solely of adult worms terminated at the same time as an infection consisting of all the parasitic stages.Immunity is not stage specific. Immunity stimulated by adult worms acts not only on adult stages inhibiting their reproduction but also inhibits the development to maturity of larvae in a challenge infection.Rats infected solely with female adult worms, whether egg producing or sterile, are more resistant to reinfection than rats infected with male worms only.Immunity stimulated by a single normal infection lasts a long time but it does not depend on the persistence of adult worms in the intestine of the rats.This work was done during the tenure of a Commonwealth Scholarship awarded by the Association of Commonwealth Universities.


Parasitology ◽  
1980 ◽  
Vol 81 (1) ◽  
pp. 17-26 ◽  
Author(s):  
B. Z. Ngwenya

SUMMARYLactating and nulliparous outbred Swiss (CF-1 strain) mice were infected at 12–16 weeks of age with Nippostrongylus brasiliensis or Trichinella spiralis. Lysophospholipase B levels in the intestinal tissue and faecal pellets were greatly depressed in infected lactating mice in contrast to infected nulliparous mice. Correlated with these depressions in lysophospholipase levels were markedly reduced numbers of bonemarrow eosinophils in infected lactating mice. Although the peak levels of lysophospholipase in the intestinal tissues occurred in both nulliparous and lactating mice by days 9 and 14 after infection with N. brasiliensis and T. spiralis, respectively, lactating mice had significantly lower lysophospholipase peak levels than nulliparous mice. The peak of luminal levels of the enzyme coincided with peak levels of the enzyme in the intestinal tissues and with theexpulsion of the majority of the worms from the small intestines of nulliparous mice. However, lactation delayed the temporal relation between the peak of lysophospholipase levels in the intestinal lumen and worm expulsion. These results suggest that lactation depressed the levels of the enzyme and interfered with its release into the intestinal lumen.


1948 ◽  
Vol 87 (6) ◽  
pp. 585-594 ◽  
Author(s):  
H. L. Ratcliffe ◽  
W. F. Wells

At intervals from 2 to 11 weeks after normal rabbits had inhaled small numbers of virulent bovine tubercle bacilli as separated cells in droplet nuclei, groups of these animals received a single exposure to reinfection during which each animal inhaled about 20,000 separated bacilli. Normal control rabbits which inhaled this large number of bacilli died within 4 weeks thereafter. Their deaths were attributed to destruction of the lungs by developing initial tubercles. Eleven of 12 rabbits which were reinfected within 4 weeks after initial infection seemed to respond as normal animals. Their lungs were largely replaced by developing reinfection tubercles when they died or were killed within 32 days after reinfection. The inflammatory response of the reinfection tubercles was not consistently different from that of initial tubercles, although reinfection tubercles contained fewer bacilli than initial lesions of the same age. Within 5 weeks after initial infection rabbits apparently had developed immunity to reinfection with virulent bovine tubercle bacilli inhaled as separated cells in droplet nuclei. In some of them, however, exposure to massive inhaled reinfection seemed to stimulate the progress of initial infection. It is suggested that in rabbits the development of resistance to tubercle bacilli does not bear a linear relationship to time, but progresses in steps and within 5 weeks after small initial infection by inhalation is adequate to prevent the growth of separated bacilli when these are deposited upon alveolar walls. It is suggested also that the basic effect of acquired resistance of rabbits to tubercle bacilli is inhibition of multiplication of the bacilli.


2021 ◽  
Vol 22 (16) ◽  
pp. 8865
Author(s):  
Huai Yang ◽  
Peigao Luo

Photosynthesis is a universal process for plant survival, and immune defense is also a key process in adapting to the growth environment. Various studies have indicated that these two processes are interconnected in a complex network. Photosynthesis can influence signaling pathways and provide both materials and energy for immune defense, while the immune defense process can also have feedback effects on photosynthesis. Pathogen infection inevitably leads to changes in photosynthesis parameters, including Pn, Gs, and Ci; biochemical materials such as SOD and CAT; signaling molecules such as H2O2 and hormones; and the expression of genes involved in photosynthesis. Some researchers have found that changes in photosynthesis activity are related to the resistance level of the host, the duration after infection, and the infection position (photosynthetic source or sink). Interactions between wheat and the main fungal pathogens, such as Puccinia striiformis, Blumeria graminis, and Fusarium graminearum, constitute an ideal study system to elucidate the relationship between changes in host photosynthesis and resistance levels, based on the accessibility of methods for artificially controlling infection and detecting changes in photosynthesis, the presence of multiple pathogens infecting different positions, and the abundance of host materials with various resistance levels. This review is written only from the perspective of plant pathologists, and after providing an overview of the available data, we generally found that changes in photosynthesis in the early stage of pathogen infection could be a causal factor influencing acquired resistance, while those in the late stage could be the result of resistance formation.


2009 ◽  
Vol 206 (13) ◽  
pp. 2947-2957 ◽  
Author(s):  
De'Broski R. Herbert ◽  
Jun-Qi Yang ◽  
Simon P. Hogan ◽  
Kathryn Groschwitz ◽  
Marat Khodoun ◽  
...  

Th2 cells drive protective immunity against most parasitic helminths, but few mechanisms have been demonstrated that facilitate pathogen clearance. We show that IL-4 and IL-13 protect against intestinal lumen-dwelling worms primarily by inducing intestinal epithelial cells (IECs) to differentiate into goblet cells that secrete resistin-like molecule (RELM) β. RELM-β is essential for normal spontaneous expulsion and IL-4–induced expulsion of Nippostrongylus brasiliensis and Heligmosomoides polygyrus, which both live in the intestinal lumen, but it does not contribute to immunity against Trichinella spiralis, which lives within IEC. RELM-β is nontoxic for H. polygyrus in vitro but directly inhibits the ability of worms to feed on host tissues during infection. This decreases H. polygyrus adenosine triphosphate content and fecundity. Importantly, RELM-β–driven immunity does not require T or B cells, alternative macrophage activation, or increased gut permeability. Thus, we demonstrate a novel mechanism for host protection at the mucosal interface that explains how stimulation of epithelial cells by IL-4 and IL-13 contributes to protection against parasitic helminthes that dwell in the intestinal lumen.


Parasitology ◽  
1979 ◽  
Vol 78 (3) ◽  
pp. 323-330 ◽  
Author(s):  
P. R. Christie ◽  
D. Wakelin ◽  
M. M. Wilson

SUMMARYThe effect of the intestinal changes brought about by the expulsion ofTrichinella spiralisin rats was studied in relation to the growth and survival of a concurrent infection withHymenolepis diminuta, a cestode not normally rejected by the rat in low-level infections. Growth ofH.diminutawas stunted in rats givenT.spiralisjust before, or after, infection withH.diminuta, the stunting being more pronounced when the cestode was given closer to the period of inflammation. There was no loss of the cestode from dual-infected rats and no evidence for destrobilation was found. LowerT.spiralisburdens had a correspondingly weaker effect on growth ofH.diminuta, and stunting was abolished by administration of the anti-inflammatory drug cortisone acetate. It is concluded that the stunting ofH.diminutais probably due to the non-specific inflammatory component of the rat's response toT.spiralisinfection.


Author(s):  
Wenjing Huang ◽  
Tsubasa S. Matsui ◽  
Takumi Saito ◽  
Masahiro Kuragano ◽  
Masayuki Takahashi ◽  
...  

Cells adapt to applied cyclic stretch (CS) to circumvent chronic activation of proinflammatory signaling. Currently, the molecular mechanism of the selective disassembly of actin stress fibers (SFs) in the stretch direction, which occurs at the early stage of the cellular response to CS, remains controversial. Here we suggest that the mechanosensitive behavior of myosin II, a major cross-linker of SFs, primarily contributes to the directional disassembly of the actomyosin complex SFs in bovine vascular smooth muscle cells and human U2OS osteosarcoma cells. First, we identified that CS with a shortening phase that exceeds in speed the inherent contractile rate of individual SFs leads to the disassembly. To understand the biological basis, we investigated the effect of expressing myosin regulatory light chain mutants and found that SFs with less actomyosin activities disassemble more promptly upon CS. We consequently created a minimal mathematical model that recapitulates the salient features of the direction-selective and threshold-triggered disassembly of SFs to show that disassembly or, more specifically, unbundling of the actomyosin bundle SFs is enhanced with sufficiently fast cell shortening. We further demonstrated that similar disassembly of SFs is inducible in the presence of an active LIM-kinase-1 mutant that deactivates cofilin, suggesting that cofilin is dispensable as opposed to a previously proposed mechanism.


2000 ◽  
Vol 18 (19) ◽  
pp. 3360-3369 ◽  
Author(s):  
Lori J. Pierce ◽  
Myla Strawderman ◽  
Steven A. Narod ◽  
Ivo Oliviotto ◽  
Andrea Eisen ◽  
...  

PURPOSE: Recent laboratory data suggest a role for BRCA1/2 in the cellular response to DNA damage. There is a paucity of clinical data, however, examining the effect of radiotherapy (RT), which causes double-strand breaks, on breast tissue from BRCA1/2 mutation carriers. Thus the goals of this study were to compare rates of radiation-associated complications, in-breast tumor recurrence, and distant relapse in women with BRCA1/2 mutations treated with breast-conserving therapy (BCT) using RT with rates observed in sporadic disease. PATIENTS AND METHODS: Seventy-one women with a BRCA1/2 mutation and stage I or II breast cancer treated with BCT were matched 1:3 with 213 women with sporadic breast cancer. Conditional logistic regression models were used to compare matched cohorts for rates of complications and recurrence. RESULTS: Tumors from women in the genetic cohort were associated with high histologic (P = .0004) and nuclear (P = .009) grade and negative estrogen (P = .0001) and progesterone (P = .002) receptors compared with tumors from the sporadic cohort. Using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity scoring, there were no significant differences in acute or chronic morbidity in skin, subcutaneous tissue, lung, or bone. The 5-year actuarial overall survival, relapse-free survival, and rates of tumor control in the treated breast for the patients in the genetic cohort were 86%, 78%, and 98%, respectively, compared with 91%, 80%, and 96%, respectively, for the sporadic cohort (P = not significant). CONCLUSION: There was no evidence of increased radiation sensitivity or sequelae in breast tissue heterozygous for a BRCA1/2 germline mutation compared with controls, and rates of tumor control in the breast and survival were comparable between BRCA1/2 carriers and controls at 5 years. Although additional follow-up is needed, these data may help in discussing treatment options in the management of early-stage hereditary breast cancer and should provide reassurance regarding the safety of administering RT to carriers of a germline BRCA1/2 mutation.


2005 ◽  
Vol 2005 ◽  
pp. 11-11 ◽  
Author(s):  
J.G.M. Houdijk ◽  
N.S. Jessop ◽  
D.P. Knox ◽  
I. Kyriazakis

Small ruminant studies have shown that a reduction in protein scarcity, through either an increase in protein supply or reduction in protein demand, results in reduced nematode egg excretion and worm burdens during the periparturient period (Houdijk and Athanasiadou, 2003). Whilst this reduced degree of parasitism indirectly suggests that such nutritional effects are mediated through changes in host immune responses, there is only limited direct evidence for this. A rodent model may be used for directly assessing immune responses that underlie nutritional control of nematode parasites. There is indirect evidence that lactating rats undergo a breakdown of immunity to the intestinal nematode Nippostrongylus brasiliensis (Houdijk et al., 2003). Provided that this breakdown is sensitive to protein nutrition, this model may be used for elucidating interactions between nutrition and immunity to parasites. Therefore, we assessed whether breakdown of immunity to N. brasiliensis in the lactating rat is sensitive to host protein nutrition.


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