Course Of Experimental Infection Research Articles

Evaluation of effects of inert vehicles proceeding from homeopathic preparation in mice’s experimental infection by Trypanosoma cruzi

Background: In experiments with homeopathic medicines is important to test the inert vehicle from succussed preparations for the treatment control. Aim: To evaluate the effect of hydro-alcoholic solutions 1cH, 6cH and 30cH in mice’s experimental infection with Trypanosoma cruzi. Methodology: In a blind, randomized, controlled test, two independent experiments with 34 and 51 swiss male mice, 8 weeks old, kept in cages micro acclimated, infected with 1400 blood trypomastigotes of the Y strain of T. cruzi (via IP), were divided: IC-untreated control; G1cH-received hydro-alcoholic solution dynamized 1cH; G6cH-received hydro-alcoholic solution dynamized 6cH and G30cH-received hydro-alcoholic solution dynamized 30cH. The solutions were prepared according to Brazilian Homeophatic Pharmacopoeia1 with alcohol 70 ° GL. Final preparations (1cH, 6cH and 30cH) were manipulated with water (Sigma-SP-Brazil). The treatment was offered diluted with water (1/100mL) ad libitum 48 hours before infection, available for 16h. After infection, the animals were treated 56h/56h for 16h until the 9th day of infection. The parasitological parameters were analyzed: Curve of Parasitemia, Total Parasitemia (TP), Peak Maximum of Parasites (PMP), Pre-Patent Period (PPP), Patent Period (PP) and Survival. The experiment was approved by the UEM’s Ethical Committee. Results: G1cH showed a higher survival (p=0.044) with a life expectancy of 2.58 times larger than the control group (Figure 1.A), as well as lower TP (p=0.002) and PMP (p = 0.018). PPP and PP showed no statistical difference, although in G1cH1 it was observed an increasing trend of PPP (p=0.065). These results are related to host’s benefit. The G6cH group presented a longer survival (p=0,045), with a life expectancy 1.94 times larger than the control group (Figure 1.B). Although no difference to TP, PMP, PP and PPP has been observed, the alcohol 6cH performed protecting animals against infection. The G30cH displayed an increasing trend of PMP (p=0.066) compared to the control group. Effects of inert vehicle succussed have been reported in studies in vitro2. However, no effects had been reported in vivo studies yet2,3. The hydro-alcoholic solution 7% 13CH, tested under the same conditions and animal model, did not change the natural evolution of the infection2. Conclusion: The hydro-alcoholic solutions 1cH and 6cH altered the course of experimental infection by T. cruzi, reducing the parasitemia and/or increasing the survival time, and can not be considered as inert vehicle in the high diluted compounds preparation.

Sensitivity of Quails (Coturnix coturnix), Siskins (Carduelis spinus), and Frogs (Rana ridibunda) to West Nile Virus.

The level of viremia and features of the course of experimental infection caused by West Nile virus were studied in two species of migratory birds, siskins Сarduelis spinus and quails Coturnix coturnix, and in one species of amphibians, frogs Rana ridibunda. In quails, the virus caused a fatal disease; histological analysis revealed pathological changes in the heart, kidneys, liver, and brain stem. In siskins and frogs, virus antigen was detected in cloacal smears despite the absence of clinical manifestations, the level of viremia was sufficient to infect insect vectors during bloodsucking. These findings suggest that siskins and frogs can be potential reservoirs of West Nile virus and play a role in its circulation.

Clinical, haematological and pathomorphological findings in Mycoplasma suis infected pigs

BackgroundMycoplasma suis (M. suis) belongs to the group of haemotrophic mycoplasmas and is known as the causative agent of infectious anaemia in pigs. In the last few years valuable insights into the mechanism of adhesion and invasion, shedding patterns and cell tropism of M. suis were gained by the use of new molecular techniques. However, details on M. suis induced lesions as well as the distribution of M. suis in different organs are still lacking. Therefore, seven splenectomised pigs were experimentally infected and clinical and laboratory investigations as well as a detailed histopathological examination were performed. Detection and quantification of M. suis DNA in blood and various tissue samples was done using a quantitative real-time PCR.ResultsDuring the course of experimental infection, periodically occurring signs of infectious anaemia of pigs including severe icteroanaemia, fever, apathy and anorexia were observed. In addition, dermatological manifestations such as haemorrhagic diathesis presenting as petechiae occurred. The most important haematological alterations were normochromic, normocytic anaemia, hypoglycaemia as well as increased bilirubin and urea concentrations. Necropsy revealed predominant evidence of haemolysis with consecutive anaemia, as well as disseminated intravascular coagulation. M. suis was found in all investigated tissues with the highest copy numbers found in the kidneys. In Giemsa stained sections M. suis was only detected red blood cell (RBC)-associated.ConclusionIn the present study, no RBC independent sequestration of M. suis was detected in organs of experimentally infected pigs. Pathological findings are most likely resulting from haemolysis, consecutive anaemia as well as from disseminated intravascular coagulation and subsequent organ impairments.

Concanavalin-A stimulates IL-17 and nitric oxide production and induces macrophage polarization and resistance to Trypanosoma cruzi infection

AimsChagas disease is a neglected tropical disease. The ability of Trypanosoma cruzi to survive within phagocytes is likely a critical factor for T. cruzi dissemination in the host. For control of the parasite load and host survival, macrophage action is required. Concanavalin-A (Con-A) presents properties that modulate immune functions and protect hosts from several experimental infectious diseases. Here, we evaluated the effects of Con-A on peritoneal macrophages as well as on the course of experimental infection by T. cruzi. Main methodsBALB/c mice, a susceptible model for T. cruzi infection, were treated with Con-A via the intraperitoneal route and 3 days later infected with T. cruzi. We quantified parasitemia, cytokines and nitric oxide (NO). Peritoneal exudate and macrophages were collected for macrophage phenotyping and cell viability, NO and cytokine detection, as well as for T. cruzi internalization and release index determination. Key findingsCon-A treatment induced IL-17a and NO production by cells from the peritoneal cavity, and M1 marker expression predominated on peritoneal macrophages. These cells are also more prone to producing TNF-α, IL-6 and NO when infected by T. cruzi and show high trypanocidal capacity. Due to a hostile peritoneal microenvironment caused by Con-A, which induces macrophage cNOS and iNOS expression, infected BALB/c mice showed reduced parasitemia and an increased survival rate. SignificanceWe conclude that Con-A can induce peritoneal M1 macrophage polarization to increase trypanocidal activity, resulting in ameliorated systemic infection in a susceptible experimental model.

Analysis of the Clinical Course of Experimental Infection with Highly Pathogenic African Swine Fever Strain, Isolated from an Outbreak in Poland. Aspects Related to the Disease Suspicion at the Farm Level.

This paper was aimed to characterize clinical signs and pathomorphological lesions in twenty-two pigs, infected intranasally by different doses of African swine fever virus (Pol18_28298_O111), isolated during the outbreak in a pig farm that occurred in Eastern Poland throughout 2018. This article also attempts to indicate risk, related to virus load and shedding, and present possible difficulties with proper disease recognition at the farm level. The results revealed that even a very low dose (5 HAU) may initiate the infection. Various forms of the disease (acute, subacute, and chronic), mainly with prodromal clinical signs like fever, apathy, and reduced feed intake were observed. The most frequently observed lesions (82%) were: hyperemia and enlargement of lymph nodes and splenomegaly. The minimal incubation period was estimated at five days post-infection (dpi). Mortality ranged from 80–100%. Two pigs survived the infection. Some viremic animals presented delayed fever. In some cases, the fever was not detectable. Shortly after viremia, the virus was secreted ion the urine, feces, and saliva. The highest levels of virus were found in the internal organs and blood; however in the case of one pig (chronic form), viral DNA was not detected in the spleen, liver, bone marrow, and brain. Veterinary diagnosis may be difficult, and the final results should always be based on laboratory investigations.

Integrative analysis of gut microbiome and metabolites revealed novel mechanisms of intestinal Salmonella carriage in chicken

Intestinal carriage of Salmonella Enteritidis (SE) in the chicken host serves as a reservoir for transmission of Salmonella to humans through the consumption of poultry products. The aim of the current study was to examine the three-way interaction that occurred between host metabolites, resident gut microbiota and Salmonella following inoculation of SE in two-week-old layer chicks. Our results revealed an overall alteration in gut microbiome and metabolites in association with SE infection. Enriched colonization by different microbial members throughout the course of experimental infection highlighted significant fluctuation in the intestinal microbial community in response to Salmonella infection. As changes in community membership occurred, there was also subsequent impact on differential regulation of interlinked predicted functional activities within the intestinal environment dictated by Salmonella-commensal interaction. Alteration in the overall microbial community following infection also has a ripple effect on the host regulation of cecum-associated metabolic networks. The findings showed that there was differential regulation in many of the metabolites in association with SE colonization in chickens. Perturbation in metabolic pathways related to arginine and proline metabolism as well as TCA cycle was most prominently detected. Taken together, the present findings provided a starting point in understanding the effect of intestinal Salmonella carriage on the microbiome and metabolome of developing young layer chicks.

High temperature induces transcriptomic changes in Crassostrea gigas that hinders progress of Ostreid herpesvirus (OsHV-1) and promotes survival.

ABSTRACTOf all environmental factors, seawater temperature plays a decisive role in triggering marine diseases. Like fever in vertebrates, high seawater temperature could modulate the host response to pathogens in ectothermic animals. In France, massive mortality of Pacific oysters, Crassostrea gigas, caused by the ostreid herpesvirus 1 (OsHV-1) is markedly reduced when temperatures exceed 24°C in the field. In the present study we assess how high temperature influences the host response to the pathogen by comparing transcriptomes (RNA sequencing) during the course of experimental infection at 21°C (reference) and 29°C. We show that high temperature induced host physiological processes that are unfavorable to the viral infection. Temperature influenced the expression of transcripts related to the immune process and increased the transcription of genes related to the apoptotic process, synaptic signaling and protein processes at 29°C. Concomitantly, the expression of genes associated with catabolism, metabolite transport, macromolecule synthesis and cell growth remained low from the first stage of infection at 29°C. Moreover, viral entry into the host might have been limited at 29°C by changes in extracellular matrix composition and protein abundance. Overall, these results provide new insights into how environmental factors modulate host–pathogen interactions.

Sm16, A Schistosoma mansoni Immunomodulatory Protein, Fails to Elicit a Protective Immune Response and Does Not Have an Essential Role in Parasite Survival in the Definitive Host.

Sm16 is an immunomodulatory protein that seems to play a key role in the suppression of the cutaneous inflammatory response during Schistosoma mansoni penetration of the skin of definitive hosts. Therefore, Sm16 represents a potential target for protective immune responses induced by vaccination. In this work, we generated the recombinant protein rSm16 and produced polyclonal antibodies against this protein to evaluate its expression during different parasite life-cycle stages and its location on the surface of the parasite. In addition, we analyzed the immune responses elicited by immunization with rSm16 using two different vaccine formulations, as well as its ability to induce protection in Balb/c mice. In order to explore the biological function of Sm16 during the course of experimental infection, RNA interference was also employed. Our results demonstrated that Sm16 is expressed in cercaria and schistosomula and is located in the schistosomula surface. Despite humoral and cellular immune responses triggered by vaccination using rSm16 associated with either Freund's or alum adjuvants, immunized mice presented no reduction in either parasite burden or parasite egg laying. Knockdown of Sm16 gene expression in schistosomula resulted in decreased parasite size in vitro but had no effect on parasite survival or egg production in vivo. Thus, our findings demonstrate that although the vaccine formulations used in this study succeeded in activating immune responses, these failed to promote parasite elimination. Finally, we have shown that Sm16 is not vital for parasite survival in the definitive host and hence may not represent a suitable target for vaccine development.

Infection kinetics and antibody responses in Deccani sheep during experimental infection and superinfection with bluetongue virus serotypes 4 and 16.

Aim:The current study was designed to understand the infection kinetics and antibody responses of major circulating serotypes of bluetongue virus (BTV) in India, i.e., BTV-4 and BTV-16 through experimental infection and superinfection of Deccani sheep, a popular breed of sheep found in the southern states of India.Materials and Methods:Experimental infection with 106 TCID50/ml BTV-4 was followed by superinfection with BTV-16 and vice versa. Along with observing for clinical signs and immunological responses in the experimentally infected sheep, the effect of infection of one specific serotype on the outcome of superinfection with a different serotype was also studied.Results:Certain interesting findings have been made in the course of experimental infection, such as prominent signs of infection in BTV-4 infection, mild or no clinical signs in BTV-16-infected and superinfected animals, and non-seroconversion of one of the BTV-16-superinfected animals. In addition, BTV was isolated from infected sheep in all the experimental conditions except BTV-16 superinfection. Furthermore, it was observed that immune response in the form of type-specific antibodies was slower with BTV-16 superinfection.Conclusion:Superinfection of a sheep with more than one serotype of BTV is a common phenomenon in BT endemic countries like India. Such situation was replicated in an experimental infection in the current study, and the findings to our knowledge are first of a kind and are likely to aid in unfolding the newer aspects of BTV pathogenesis and virulence.

Kinetics of Genetic Variation of the Mycoplasma genitalium MG192 Gene in Experimentally Infected Chimpanzees.

Mycoplasma genitalium, a human pathogen associated with sexually transmitted diseases, is capable of causing chronic infections, though mechanisms for persistence remain unclear. Previous studies have found that variation of the MgPa operon occurs by recombination of repetitive chromosomal sequences (known as MgPars) into the MG191 and MG192 genes carried on this operon, which may lead to antigenic variation and immune evasion. In this study, we determined the kinetics of MG192 sequence variation during the course of experimental infection using archived specimens from two chimpanzees infected with M. genitalium strain G37. The highly variable region of MG192 was amplified by PCR from M. genitalium isolates obtained at various time points postinfection (p.i.). Sequence analysis revealed that MG192 sequence variation began at 5 weeks p.i. With the progression of infection, sequence changes accumulated throughout the MG192 variable region. The presence of MG192 variants at specific time points was confirmed by variant-specific PCR assays and sequence analysis of single-colony cloned M. genitalium organisms. MG192 nucleotide sequence variation correlated with estimated recombination events, predicted amino acid changes, and time of seroconversion, a finding consistent with immune selection of MG192 variants. In addition, we provided evidence that MG192 sequence variation occurred during the process of M. genitalium single-colony cloning. Such spontaneous variation suggests that some MG192 variation is independent of immune selection but may form the basis for subsequent immune selection.

Trans-species communication in the Mycobacterium tuberculosis-infected macrophage.

Much of the infection cycle of Mycobacterium tuberculosis (Mtb) is spent within its host cell, the macrophage. As a consequence of the chronic, enduring nature of the infection, this cell-cell interaction has become highly intimate, and the bacterium has evolved to detect, react to, and manipulate the evolving, immune-modulated phenotype of its host. In this review, we discuss the nature of the endosomal/lysosomal continuum, the characterization of the bacterium's transcriptional responses during the infection cycle, and the dominant environmental cues that shape this response. We also discuss how the metabolism of both cells is modulated by the infection and the impact that this has on the progression of the granuloma. Finally, we detail how these transcriptional responses can be exploited to construct reporter bacterial strains to probe the temporal and spatial environmental shifts experienced by Mtb during the course of experimental infections. These reporter strains provide new insights into the fitness of Mtb under immune- and drug-mediated pressure.

Course of experimental infection of canine leishmaniosis: Follow-up and utility of noninvasive diagnostic techniques

This study compares the utility of a molecular diagnosis of experimental CanL on non-invasive samples (urine, conjunctival (CS), oral (OS) and vulvar (VS) swabs) with that of traditional invasive techniques during the course of infection. Eight dogs were experimentally infected with Leishmania infantum and followed monthly for 12 months to assess clinical, clinicopathological, immunological and parasitological variables. Active infection was produced in 100% of the dogs. The animals showed positive bone marrow (BM) cytologies and cultures, clinical signs, clinicopathological abnormalities and a high specific humoral immune response. The infection was detected at 90 days post-infection (p.i.) by real-time quantitative PCR (rtQ-PCR) on BM in all dogs and in blood in 2 dogs, while anti-L. infantum antibody seroconversion occurred between Days 120 and 180 days p.i. The tissue with the highest L. infantum kDNA load, as detected by rtQ-PCR, was BM (range 381.5–70,000 parasites/ml at the study end), this sample type showing greater sensitivity than peripheral blood (PB). The vulvar swabs used here for the first time to quantify parasite loads in dogs revealed a greater load than oral and conjunctival swabs at one year p.i. Urine samples showed the lowest concentrations of L. infantum DNA (maximum: 8.57 parasites/ml). Our results suggest that for the early detection of infection, adding to serology a test such as rtQ-PCR on OS or VS improves sensitivity and specificity.

Hematological and parasitological changes in mice experimentally infected by Trypanosoma cruzi and treated with biotherapy 7dH

IntroductionBiotherapies prepared from Trypanosoma cruzi alter the course of experimental infection by this protozoan, this encouraged the study of these highly diluted medications. The work aimed to evaluate parasitological and hematological parameters in mice experimentally infected by Trypanosoma cruzi and treated with T. cruzi biotherapy 7dH. MethodologyA blind randomized controlled study was performed using Swiss mice infected with 1400 trypomastigotes of the Y strain—T. cruzi and divided: IC (infection control treated with water), CTBZ (control treated with benznidazole), and TBB7dH30 (treated with biotherapy T. cruzi 7dH, 30 days before infection). Parasitological parameters were evaluated daily from day 4 of infection until death of animals, and hematological parameters were evaluated on day 0, 4, 8, and 12. ResultsThe TBB7dH30 group had a higher parasitemia peak, with no changes in total parasitemia. The number of red blood cells, hematocrit and hemoglobin values were reduced earlier than the other groups. However, on day 12 of infection, hematocrit and hemoglobin values were higher compared to IC group. Leukocyte counts were significantly reduced only on day 8 of infection. Similar outcome was obtained in the differential lymphocyte count. Despite eosinophilia, no variation in the amount of these cells was observed during the course of infection, in contrast to IC and CTBZ groups. ConclusionsThe administration of T. cruzi biotherapy 7dH 30 days before infection altered the experimental course of infection by T. cruzi and hematological parameters. However, further studies are necessary that allow confirming the immunomodulatory effects of biotherapy.

Clinical and haematological characterisation of Mycoplasma suis infections in splenectomised and non-splenectomised pigs

Mycoplasma suis causes infectious anaemia in pigs (IAP), which can manifest in various degrees of severity depending on the virulence and the host‘s susceptibility. As M. suis cannot be cultured in vitro experimental infections of splenectomised animals play an essential role for pathogenesis research. The aim of the present study was to characterise the course of experimental infection using the highly virulent and red blood cell (RBC-) invasive M. suis strain KI3806, to compare the experimental course in splenectomised and non-splenectomised pigs and to correlate clinical and haematological parameters with M. suis blood loads. All infected splenectomised pigs (n=7) were PCR-positive 2 days post infection (DPI) with maximum mean bacterial loads of 1.61×1010M. suis/mL on 8 DPI. They developed severe anaemia and massive hypoglycaemia by 8 DPI and had to be euthanised preterm (until 8 DPI) without seroconversion. The non-splenectomised pigs (n=7) became PCR-positive within 23 DPI and reached a maximum mean M. suis load of 1.64×105M. suis/mL on 8 DPI. They developed mild anaemia, massive skin alterations with petechiae and haemorrhagic diathesis and seroconverted within 35 DPI.The study demonstrated that experimental infection of splenectomised pigs with the highly virulent M. suis strain KI3806 induces a fulminant course of infection. In contrast, M. suis strain KI3806 induces a mild course of disease in non-splenectomised pigs, which resembles the situation in naturally infected pigs. Therefore, these infection models are valuable for future pathogenesis studies on acute and chronic M. suis infections.

Flow cytometry detection of infectious pancreatic necrosis virus (IPNV) within subpopulations of Atlantic salmon (Salmo salar L.) leucocytes after vaccination and during the time course of experimental infection

In the present study, intracellular infectious pancreatic necrosis virus (IPNV) in salmon leucocytes was detected by flow cytometry after experimental cohabitant challenge. IPNV vaccinated, non-vaccinated and intraperitoneally (i.p.) infected salmon (virus shedders) were analysed at different times throughout the period when mortality occurred. Fish that had survived 61 days post challenge (carriers) were also analysed. In particular, we analysed the presence of IPNV in B-cells (C7G7+cells) and in neutrophils (E3D9+ cells) in head kidney leucocytes (HKL) and in peripheral blood leucocytes (PBL).IPNV was present in HKL and PBL from all challenged fish groups at all samplings, including carriers. IPNV was also found intracellular in other leucocytes than B-cells and neutrophils. During the time course of infection there were changes in proportion of B-cells and neutrophils and in proportions of IPNV+ cells. In vaccinated fish, a delay in the changes observed in the proportion of IPNV+ cells and in the proportions of the two subpopulations was identified. The vaccinated fish were protected against disease as no fish died compared to 30.8% of non-vaccinated cohabitant fish. All i.p. infected fish, except one, survived the challenge. This is consistent with previous studies and confirmed that the routes of infection can influence mortality. The analyses in this study could not identify any factors enlightening this absence of mortality in i.p. infected fish, but both flow cytometry and qRT-PCR showed that i.p. infected fish were carriers of IPNV. The present study also found that IPNV was present in both B-cells and neutrophils as well as in other leucocytes in all carriers after cohabitant challenge. These fish had survived 9 weeks post challenge and 4 weeks after mortality has ceased. The fish harbouring virus within their leucocytes might become life long carriers and represent a risk for disease outbreaks, being virus shedders. Such fish are protected from later infections if the virus exposure has resulted in protective immunity. Flow cytometry was found to be very suitable for detection of intracellular virus after in vivo challenge and the sensitivity was demonstrated by the detection of virus in carriers.

Toxocara-induced hepatic inflammation: Immunohistochemical characterization of lymphocyte subpopulations and Bcl-2 expression

Toxocariasis is a soil-transmitted helminthic disease due to infection of humans by larvae of Toxocara canis (T. canis). It is one of the most commonly reported zoonotic infections in the world. The aim of this study was to characterize the key immune cells and activity of Bcl-2 in hepatic inflammation during the course of experimental infection by T. canis. Mice experimentally infected with T. canis were divided into two groups: mice with primary infection by Toxocara, and those infected after sensitization by Toxocara excretory-secretory antigen. CD4+, CD8+, and Bcl-2-expressing T lymphocytes were identified in the liver by immunohistochemistry at different durations post-infection. Recruitment of both CD4+ and CD8+ T lymphocytes within the inflammatory reaction in the liver was observed, with difference in count and localization. These cells were detected within and around Toxocara-induced granulomas as well as in isolated inflammatory foci in the portal tracts or within the hepatic parenchyma. The antiapoptotic protein Bcl-2 showed no significant change at different periods post-infection. On the other hand, immunization of mice with Toxocara excretory-secretory antigen prior to experimental infection caused earlier and more pronounced recruitment of CD4+ and CD8+ T cells to the liver and enhanced expression of Bcl-2. Moreover, CD8+ cells became more diffuse within the inflammatory infiltrate. These results suggest a dynamic change in key immune cells according to the duration of infection as well as the immune status of the host.

Probiotics in carp fish nutrition

Uncontrolled use of antibiotics in aquaculture caused the appearance and spreading of pathogens resistance to antibiotics, what consequently drove up to the necesity of finding new technologies for protecting aquatic organisms from pathogens. Probiotics are aimed to reduce antibiotics application, and furthermore they have an important role not only in disease prevention but also in efficiency of food utilization and improvement of production parameters. Carp fish species are economically most significant in Republic of Serbia, therefore this work summarizes the results of previous studies of antibiotics application in this kind in particular. There is also pointed out to numerous harmful side effects of antibiotics use in aquaculture, and described the previous results of investigations on mechanism of probiotics effects and specificity of their use in this field as well. Beside this, there are summarized the results that show positive influence of probiotics in cyprinides nutrition on production performance, haematological parameters, course of experimental infection, activity of digestive enzymes. Special attention is paid to criteria for proper selection of probiotics in cyprinides production.

Experimental and natural infections in MyD88‐ and IRAK‐4‐deficient mice and humans

Most Toll‐like‐receptors (TLRs) and interleukin‐1 receptors (IL‐1Rs) signal via myeloid differentiation primary response 88 (MyD88) and interleukin‐1 receptor‐associated kinase 4 (IRAK‐4). The combined roles of these two receptor families in the course of experimental infections have been assessed in MyD88‐ and IRAK‐4‐deficient mice for almost fifteen years. These animals have been shown to be susceptible to 46 pathogens: 27 bacteria, eight viruses, seven parasites, and four fungi. Humans with inborn MyD88 or IRAK‐4 deficiency were first identified in 2003. They suffer from naturally occurring life‐threatening infections caused by a small number of bacterial species, although the incidence and severity of these infections decrease with age. Mouse TLR‐ and IL‐1R‐dependent immunity mediated by MyD88 and IRAK‐4 seems to be vital to combat a wide array of experimentally administered pathogens at most ages. By contrast, human TLR‐ and IL‐1R‐dependent immunity mediated by MyD88 and IRAK‐4 seems to be effective in the natural setting against only a few bacteria and is most important in infancy and early childhood. The roles of TLRs and IL‐1Rs in protective immunity deduced from studies in mutant mice subjected to experimental infections should therefore be reconsidered in the light of findings for natural infections in humans carrying mutations as discussed in this review.

Response of mice to continuous 5-day passive hyperthermia resembles human heat acclimation.

Chronic repeated exposure to hyperthermia in humans results in heat acclimation (HA), an adaptive process that is attained in humans by repeated exposure to hyperthermia and is characterized by improved heat elimination and increased exercise capacity, and acquired thermal tolerance (ATT), a cellular response characterized by increased baseline heat shock protein (HSP) expression and blunting of the acute increase in HSP expression stimulated by re-exposure to thermal stress. Epidemiologic studies in military personnel operating in hot environments and elite athletes suggest that repeated exposure to hyperthermia may also exert long-term health effects. Animal models demonstrate that coincident exposure to mild hyperthermia or prior exposure to severe hyperthermia can profoundly affect the course of experimental infection and injury, but these models do not represent HA. In this study, we demonstrate that CD-1 mice continuously exposed to mild hyperthermia (ambient temperature ~37°C causing ~2°C increase in core temperature) for 5days and then exposed to a thermal stress (42°C ambient temperature for 40min) exhibited some of the salient features of human HA, including (1) slower warming during thermal stress and more rapid cooling during recovery and (2) increased activity during thermal stress, as well as some of the features of ATT, including (1) increased baseline expression of HSP72 and HSP90 in lung, heart, spleen, liver, and brain; and (2) blunted incremental increase in HSP72 expression following acute thermal stress. This study suggests that continuous 5-day exposure of CD-1 mice to mild hyperthermia induces a state that resembles the physiologic and cellular responses of human HA. This model may be useful for analyzing the molecular mechanisms of HA and its consequences on host responsiveness to subsequent stresses.

Kinetics of Foxp3-expressing regulatory cells in experimental Toxocara canis infection

Foxp3-expressing cells have recently been recognized as a cornerstone for the homeostasis of the immune system, and as key cells in many infectious diseases. Moreover, they have been found to contribute to the regulation of parasite-induced immunopathology in many parasitic infections. However, their role in Toxocara-induced immunopathology has not yet been investigated. The aim of this study is to assess the kinetics of Foxp3-expressing regulatory cells during the course of experimental infection by Toxocara canis (T. canis). Foxp3+ cells were identified in the liver by immunohistochemistry, and splenic Foxp3 gene expression was evaluated. We found significantly progressive increase in Foxp3-expressing cell counts in the liver starting from 5weeks p.i. These cells were detected within and around Toxocara-induced granulomas as well as in isolated inflammatory foci in the portal tracts or within the hepatic parenchyma. Likewise, expression of Foxp3 mRNA in the spleen significantly increased at 5 and 16weeks p.i. Furthermore, immunization of mice with Toxocara excretory–secretory antigen prior to experimental infection caused earlier mobilization and recruitment of Foxp3+ cells to the liver and enhanced splenic expression of Foxp3 transcripts. These results suggest a potential role of Foxp3-expressing regulatory cells in the evolution of the immunopathological events during infection by T. canis.