肝癌术后早期应用胸腺肽α 1对T淋巴细胞亚群的影响

目的：探讨肝癌患者术后早期应用胸腺肽α1对T淋巴细胞亚群的影响。方法： 46例肝癌手术患者, 随机分治疗组（23例）和对照组（23例）, 治疗组于术后1、3、5 d皮下注射胸腺肽α1 1.6 mg,观察2组术前后第1、4、7 d CD3+、CD4+、CD8+、CD4+/CD8+的变化情况。结果：（1）组内比较：对照组术后CD4+、CD4+/CD8+低于术前（P<0.05）,术后第1、4、7 d CD8+高于手术前（P<0.05）。治疗组CD3+、CD4+、 CD4+/CD8+术后与术前相比无显著差异;CD3+、CD4+/CD8+术后第1、7 d比较有显著差异（P<0.05）。（2）组间比较：CD4+、CD4+/CD8+治疗组高于对照组（术后第1、4、7 d均P<0.05）,治疗组CD8+细胞百分率低于对照组（术后第1、4、7 d均P<0.05）;治疗组CD3+细胞百分率高于对照组（术后第4、7 d P<0.05）。结论： 手术对肝癌患者术后T淋巴细胞免疫功能有抑制作用,胸腺肽α1对T淋巴细胞免疫功能有调节作用。     

Isoform localization of Dectin‐1 regulates the signaling quality of anti‐fungal immunity

Dectin‐1 is recognized as a major receptor for fungal ß‐glucans and contributes to anti‐fungal immunity. Human monocyte populations express Dectin‐1 isoforms A and B, which differ by the presence of a stalk region and its N‐linked glycosylation site. Here, we analyzed the expression of both isoforms in human monocyte‐derived cells. The cellular localization on cell lines stably expressing either Dectin‐1 isoform A or B was studied by flow cytometry and confocal laser scanning microscopy. Intracellular protein signaling and cytokine production were analyzed by immunoblotting and cytometric bead array, respectively. Monocyte‐derived cells showed cell type‐specific expression of the two isoforms. Glycosylated Dectin‐1 isoform A was predominantly localized at the cell surface, non‐glycosylated isoform B was retained intracellularly. Inhibition of glycosylation resulted in efficient abrogation of cell surface expression of isoform A. Signaling quality following Dectin‐1 stimulation was reduced in isoform B cells. Differential isoform specific cytokine secretion was observed by cytometric bead array. We show here that n‐glycosylation of Dectin‐1 is crucial for its cell surface expression and consequently signal transduction. Taken together, unique cytokine secretion and varying expression levels of human Dectin‐1 isoforms on monocyte‐derived cells may indicate distinct isoform usage as a cell type‐specific mechanism of regulating anti‐fungal immunity.     

Immune checkpoint inhibitors in multiple myeloma: A review of the literature

The human immune system has structures called checkpoints controlling the intensity and the duration of immune responses. In the last years, studies and research have been concentrating on creating new drugs recognized as Immune Checkpoint Inhibitors that have been launched in clinical practice to treat patients with several types of cancer, including multiple myeloma. Multiple myeloma is characterized by dysfunctions in humoral and cellular immunity altering immune surveillance and support tumor advancement to escape: in particular, the disease causes the inactivation of T-cells because of their bond with antigens shown in cancer cells. It can be stated that checkpoint inhibitors “inhibit the inhibition” of cell-mediated immunity and induce tumor cells apoptosis. In this review we have focused our attention on summarizing current information about Immune Checkpoint Inhibitors which have been developed in the last years to treat multiple myeloma; particular consideration will be dedicated to describing their mechanism of action and their potential use in therapy. Further investigations are necessary in this field to define the possibility of an effective and safe inclusion of these drugs in clinical practice.     

Immunogenetics of type 1 diabetes: A comprehensive review

Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing beta cells in the pancreas. Prevention of T1D will require the ability to detect and modulate the autoimmune process before the clinical onset of disease. Genetic screening is a logical first step in identification of future patients to test prevention strategies. Susceptibility to T1D includes a strong genetic component, with the strongest risk attributable to genes that encode the classical Human Leukocyte Antigens (HLA). Other genetic loci, both immune and non-immune genes, contribute to T1D risk; however, the results of decades of small and large genetic linkage and association studies show clearly that the HLA genes confer the most disease risk and protection and can be used as part of a prediction strategy for T1D. Current predictive genetic models, based on HLA and other susceptibility loci, are effective in identifying the highest-risk individuals in populations of European descent. These models generally include screening for the HLA haplotypes “DR3” and “DR4.” However, genetic variation among racial and ethnic groups reduces the predictive value of current models that are based on low resolution HLA genotyping. Not all DR3 and DR4 haplotypes are high T1D risk; some versions, rare in Europeans but high frequency in other populations, are even T1D protective. More information is needed to create predictive models for non-European populations. Comparative studies among different populations are needed to complete the knowledge base for the genetics of T1D risk to enable the eventual development of screening and intervention strategies applicable to all individuals, tailored to their individual genetic background. This review summarizes the current understanding of the genetic basis of T1D susceptibility, focusing on genes of the immune system, with particular emphasis on the HLA genes.     

Nuclear localization of the tyrosine kinase Itk and interaction of its SH3 domain with karyopherin alpha (Rch1alpha)

We report a physical and functional association between the Tec-family tyrosine kinase Itk (Emt/Tsk) and the nuclear import chaperone karyopherin alpha (Rch1alpha) in human T cells. The Itk-SH3 domain and the Rch1alpha proline-rich (PR) motif were crucial for the Itk/Rch1alpha constitutive interaction as demonstrated by directed mutagenesis of the Rch1alpha PR motif (proline 242 to alanine, P242A). TCR-CD3 stimulation of Jurkat T cells resulted in increased Itk/Rch1alpha complex formation, recruitment of karyopherin beta to the protein complex and Rch1alpha tyrosine phosphorylation. Analysis of in vitro kinase reactions with a panel of recombinant glutathione-S-transferase (GST) fusion tyrosine kinases (Itk, Lck, ZAP-70 and Jak3) revealed that only GST-Itk efficiently phosphorylated a recombinant GST-Rch1alpha fusion. We observed constitutive nuclear localization of Itk that was up-regulated following either TCR-CD3 stimulation or over-expression of wild-type Rch1alpha in T cells. Further, nuclear localization of Itk and TCR-CD3-mediated IL-2 production were significantly down-regulated following expression of the Rch1alpha-P242A mutant, implicating a role for Rch1alpha in the nuclear translocation of Itk.     

Characterizing the inclusion of pregnant and breastfeeding people in infectious diseases randomized controlled trials: a targeted literature review

ObjectivesSevere complications of infectious diseases can occur during pregnancy. Evidence-based prevention and treatment strategies are critical to improve maternal and neonatal health outcomes. Despite this medical need, pregnant and breastfeeding people have been systematically excluded from biomedical research. The objective of this study was to characterize representation of pregnant and breastfeeding people in randomized controlled trials (RCTs) evaluating a broad range of interventions for infectious diseases.MethodsPregnancy and breastfeeding inclusion criteria were examined in infectious diseases RCTs published between 1 January 2017, and 31 December 2019, in the top five highest impact general medicine and the top three highest impact infectious diseases and HIV journals.ResultsOf 376 RCTs, 5.3% and 1.9% included pregnant and breastfeeding people, respectively. Justification for exclusion was documented in 36/271 (13.3%) studies that explicitly excluded pregnant people. Most studies excluding pregnant people (177/271, 65.3%) required at least one form of contraception, abstinence and/or negative pregnancy test(s) as part of participation. Only 11/271 (4.1%) studies excluding pregnant people allowed participants to continue the intervention if unintended pregnancy occurred during the study. When both pregnant and non-pregnant people were eligible, pregnant people made up <3% of participants. Only 2/48 (4.2%) vaccine studies included pregnant people; 13/234 (5.5%) drug studies included pregnant people. All studies of procedures, devices, behaviour/education and supplements/vitamins explicitly excluded or did not address pregnancy eligibility criteria. Only 2/20 (10.0%) RCTs including pregnant people collected pharmacokinetic data.DiscussionThis study demonstrates widespread exclusion of pregnant and breastfeeding people from infectious disease RCTs.     

Extracellular vesicles and asthma: A review of the literature

Asthma is a chronic, recurrent and incurable allergy‐related respiratory disease characterized by inflammation, bronchial hyperresponsiveness and narrowing of the airways. Extracellular vesicles (EVs) are a universal feature of cellular function and can be detected in different bodily fluids. Recent evidence has shown the possibility of using EVs in understanding the pathogenesis of asthma, including their potential as diagnostic and therapeutic tools. Studies have reported that EVs released from key cells involved in asthma can induce priming and activation of other asthma‐associated cells. A literature review was conducted on all current research regarding the role and function of EVs in the pathogenesis of asthma via the PRISMA statement method. An electronic search was performed using EMBASE and PubMed through to November 2018. The EMBASE search returned 76 papers, while the PubMed search returned 211 papers. Following duplicate removal, titles and abstracts were screened for eligibility with a total of 34 studies included in the final qualitative analysis. The review found evidence of association between the presence of EVs and physiological changes characteristic of asthma, suggesting that EVs are involved in the pathogenesis, with the weight of evidence presently favouring deleterious effects of EVs in asthma. Numerous studies highlighted differences in exosomal contents between EVs of healthy and asthmatic individuals, which could be employed as potential diagnostic markers. In some circumstances, EVs were also found to be suppressive to disease, but more often promote inflammation and airway remodelling. In conclusion, EVs hold immense potential in understanding the pathophysiology of asthma, and as diagnostic and therapeutic markers. While more research is needed for definitive conclusions and their application in medical practice, the literature presented in this review should encourage further research and discovery within the field of EVs and asthma.     

Immunogenetics of systemic lupus erythematosus: A comprehensive review

Our understanding of the genetic basis of systemic lupus erythematosus has progressed rapidly in recent years. While many genetic polymorphisms have been associated with disease susceptibility, the next major step involves integrating these genetic polymorphisms into the molecular mechanisms and cellular immunology of the human disease. In this review, we summarize some recent work in this area, including the genetics of the type I IFN response in SLE, including polygenic and monogenic factors, as well as epigenetic influences. Contributions of both HLA and non-HLA polymorphisms to the complex genetics of SLE are reviewed. We also review recent reports of specific gene deficits leading to monogenic SLE-like syndromes. The molecular functions of common SLE-risk variants are reviewed in depth, including regulatory variations in promoter and enhancer elements and coding-change polymorphisms, and studies which are beginning to define the molecular and cellular functions of these polymorphisms in the immune system. We discuss epigenetic influences on lupus, with an emphasis on micro-RNA expression and binding, as well as epigenetic modifications that regulate the expression levels of various genes involved in SLE pathogenesis and the ways epigenetic marks modify SLE susceptibility genes. The work summarized in this review provides a fascinating window into the biology and molecular mechanisms of human SLE. Understanding the functional mechanisms of causal genetic variants underlying the human disease greatly facilitates our ability to translate genetic associations toward personalized care, and may identify new therapeutic targets relevant to human SLE disease mechanisms.     

1型葡萄糖转运体缺陷综合征一例报告及文献复习

目的总结1型葡萄糖转运体缺陷综合征的临床特点、实验室检查、分子遗传学诊断及生酮饮食治疗疗效。方法报告1例以痫样发作为首发的1型葡萄糖转运体缺陷综合征病例。检索国内外相关文献,共检索出明确诊断的1型葡萄糖转运体缺陷综合征32例,进行文献复习。结果包括作者报告1例患者,共33例,男19例,女14例。临床特点:27/33例有痫样发作,发作年龄2个月至35岁之间。大多发作年龄在6个月以内。25/33例有共济失调,大多数轻中度共济失调,少部分患者共济失调影响行走及日常生活。24/33例肌张力障碍。14/33例有小头畸形。实验室检查:30/33例患者进行了脑脊液糖检查,23-56mg/dl之间,平均34.2±4.7mg/dl。脑脊液糖/血糖0.24-0.57之间,平均0.38±0.07。21/33例患者进行了红细胞摄取3-O-甲基-D-葡萄糖的能力检查,结果显示红细胞摄取3-O-甲基-D-葡萄糖的能力较正常对照下降约50%左右。29/33例进行了脑电图检查,发现痫样放电25例,表现为多灶性棘波、棘慢波。32/33例患者进行了GLUT1-DS基因SLC2A1筛查,发现12例错义突变,2例无义突变,2例插入突变,16例缺失或剪切位点突变。治疗:所有癫痫患者均进行了抗癫痫药物治疗,痫样发作均难以控制。28/33例患者(25例癫痫患者和3例发作性运动障碍)进行了生酮饮食治疗。24例癫痫患者的痫样发作完全控制,1例痫样发作明显缓解。3例发作性运动障碍明显改善。结论 1型葡萄糖转运体缺陷综合征临床以难治性痫样发作、语言智能发育落后、脑脊液糖/血糖明显降低为特点,常规抗癫痫药物难以控制痫样发作,生酮饮食能够控制痫样发作,并对语言、认知、运动障碍均有改善作用。     

The immunogenetics of primary biliary cirrhosis: A comprehensive review

Primary biliary cirrhosis (PBC), a classic autoimmune liver disease, is characterised by a progressive T cell predominant lymphocytic cholangitis, and a serologic pattern of reactivity in the form of specific anti-mitochondrial antibodies (AMA). CD4+ T cells are particularly implicated by PBC's cytokine signature, the presence of CD4+ T cells specific to mitochondrial auto-antigens, the expression of MHC II on injured biliary epithelial cells, and PBC's coincidence with other similar T cell mediated autoimmune conditions. CD4+ T cells are also central to current animal models of PBC, and their transfer typically also transfers disease. The importance of genetic risk to developing PBC is evidenced by a much higher concordance rate in monozygotic than dizygotic twins, increased AMA rates in asymptomatic relatives, and disproportionate rates of disease in siblings of PBC patients, PBC family members and certain genetically defined populations. Recently, high-throughput genetic studies have greatly expanded our understanding of the gene variants underpinning risk for PBC development, so linking genetics and immunology. Here we summarize genetic association data that has emerged from large scale genome-wide association studies and discuss the evidence for the potential functional significance of the individual genes and pathways identified; we particularly highlight associations in the IL-12-STAT4-Th1 pathway. HLA associations and epigenetic effects are specifically considered and individual variants are linked to clinical phenotypes where data exist. We also consider why there is a gap between calculated genetic risk and clinical data: so-called missing heritability, and how immunogenetic observations are being translated to novel therapies. Ultimately whilst genetic risk factors will only account for a proportion of disease risk, ongoing efforts to refine associations and understand biologic links to disease pathways are hoped to drive more rational therapy for patients.     

Correlation between C9ORF72 mutation and neurodegenerative diseases: A comprehensive review of the literature

Chromosome 9 open reading frame 72 (C9ORF72) encodes a 54-kDa protein with unknown function that is expressed at high levels in the central nervous system. The C9ORF72 hexanucleotide amplification is one of the most recently discovered repetitive amplification diseases related to neurodegeneration. Its association with amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) spectrum diseases has been fully established, although a causative role for C9ORF72 in Alzheimer''s disease (AD) and Parkinson''s disease (PD) remains to be established. Therefore, in this article, we will review the evidence for C9ORF72 as a causative factor in neurodegenerative diseases, the underlying mechanisms, and the potential for targeting C9ORF72 as a strategy to alleviate neurodegenerative disease progression.     

Transendothelial migration confers a survival advantage to activated T lymphocytes: role of LFA-1/ICAM-1 interactions

The clearance of activated T lymphocytes by apoptosis is an essential component in the resolution of the immune response; however, certain signals received within inflamed tissue may result in the persistence of activated T cells. Our previous work has shown that, when compared with resting cells, effector cells migrate more efficiently across endothelium, thus such cells may be selectively recruited to sites of inflammation. We hypothesized that transmigration of T cells across endothelium might influence cell survival. We have generated T cell lines by culturing in IL-2 following PHA activation. These T cell lines die rapidly by apoptosis when deprived of IL-2 (53.7 +/- 4.0% survival after 24 h). In contrast, cells that have migrated across human umbilical vein endothelial cells (HUVEC) survived significantly better than control cells (80.3 +/- 3.6%, n= 18, P<0.001). Endothelial cell conditioned medium was also able to reduce apoptosis, but this effect was small when compared with the protective effect of transmigration. Culture of T lymphocytes on fibronectin, or RGD peptides, or in suspension with a range of chemokines active on T cells, including RANTES and lymphotactin had no effect on survival. In contrast, blocking LFA-l/ICAM-l interactions reduced the protective effect of transmigration (42.3 +/- 6.7% reduction). Culture of activated T cells on immobilized ICAM-l alone also increased survival. These results indicate that signals received by activated T cells during extravasation can influence their subsequent survival within tissue, and implicates the involvement of LF A-l/ICAM-l interactions.     

Roles of alpha(4) integrins/VCAM-1 and LFA-1/ICAM-1 in the binding and transendothelial migration of T lymphocytes and T lymphoblasts across high endothelial venules

Several cell adhesion molecules that mediate the binding of lymphocytes to high endothelial venules (HEV) from flowing blood have been identified but the regulation of lymphocyte migration across the HEV wall into the lymph node (LN) is far from understood. In this study we have used an in vitro model of lymphocyte migration across HEV, and analysed the roles of two integrins in the binding and transendothelial migration of T lymphocytes and T lymphoblasts. The adhesion of T lymphocytes to high endothelial cells (HEC) cultured from rat LN HEV differed from that of T lymphoblasts since the percentage of T lymphoblasts that adhered and transmigrated was higher and was not increased by IFN-gamma pretreatment of HEC. Antibodies to alpha(4) integrins, VCAM-1 or LFA-1 maximally inhibited T lymphocyte adhesion by 40-50%, whereas antibodies to ICAM-1 were less effective (<20% inhibition). The effects of alpha(4) integrin and LFA-1 antibodies were additive, giving >90% inhibition. T lymphocytes which adhered in the presence of LFA-1 antibody showed reduced levels of transmigration and, in the presence of alpha(4) integrin antibody, slightly increased transmigration. Antibodies to alpha(4) integrins, VCAM-1, LFA-1 or ICAM-1 had little effect on T lymphoblast adhesion (maxima of 10-30% inhibition) and T lymphoblasts transmigrated normally in the presence of either alpha(4) integrin or LFA-1 antibodies. However, the effects of alpha(4) integrin and LFA-1 antibodies on T lymphoblast adhesion were synergistic, giving >90% inhibition of adhesion. These results suggest that the majority of T lymphoblasts use either alpha(4) integrins or LFA-1 to bind and transmigrate HEV, and the roles of these integrins on activated T cells are overlapping and redundant. In contrast, either integrin supports half-maximal binding of unactivated T lymphocytes to the surface of HEV and LFA-1 makes a larger contribution than alpha(4) integrins to transendothelial migration.     

Involvement of {alpha}1 and {alpha}4 integrins in gut mucosal injury of graft-versus-host disease

We have investigated the involvement of adhesion molecules inthe lymphocyte infiltration associated with acute intestinalgraft-versus-host disease (GVHD) induced by injection of C3Hlymph node cells into irradiated (C3H x DBA/2)F₁ mice. Firstwe analyzed the expression profile of adhesion molecules including1, 2, 4, 5, 6, L and ß7 integrins, CD44 and L-selectinof lymphocytes from lymph nodes and gut mucosa in normal mice.In normal mice, intraepithelial lymphocytes (IEL) and laminapropria lymphocytes (LPL) uniquely showed increased expressionof 1, 2 and ß7 integrins, and decreased expressionof L-selectin compared with that of lymphocytes of the lymphnodes and Peyer's patches. In mice with GVHD, IEL and LPL ofdonor lymph node cells origin underwent phenotyplc changes characterizedby the increased expression of 1, L and ß7 integrins,and the loss of L-selectin. The expression profile of adhesionmolecules on IEL and LPL of GVHD mice resembled that of normalmice except for the lack of 2 integrin. Treatment of GVHD micewith anti-1,-4 or-ß7 integrin antibody alone partiallyprevented the mucosal pathology of intestinal GVHD, whereasonly mice treated with anti-1 showed reduced donor lymphocyticinfiltration into the intestinal mucosa. In contrast, treatmentwith anti-L or anti-CD44 antibody did not affect the intestinalGVHD. Furthermore, dual blockade of both 1 and 4 integrins completelyinhibited the mucosal pathology and donor lymphocyte infiltrationof intestinal GVHD. These results indicate that 1 and 4 integrinsplay an important role in the pathology of intestinal GVHD.     

血浆交换治疗四种免疫性疾病的机理和疗效检测的初步探讨

本文介绍血浆交换(plasma exchange,PE)治疗8例四种免疫性疾病,应用PE前后测定外周血T细胞集落数、单克隆抗体(monoclone antibody,McAb)对T细胞亚群的标记和循环免疫复合物(circulating immune complex,CIC)的改变及其相互间关系的比较,探索PE产生疗效的机理和检测疗效的指标。实验资料提示,PE后机体内有害抗体、CIC的清除、细胞免疫功能的词正等均属产生疗效的机理,系综合性的作用。检测疗效的指标有T细胞集落数(TL-CFU)、CIC值和T_H与T_S比值的恢复。PE后CIC下降、T_H上升,与PE前相比其P值均<0.01。而换浆后含有病人血浆及血清成份的T细胞集落数的恢复正常,对检测PE后的疗效尤为敏感、确切。     

A role for the histone H2A deubiquitinase MYSM1 in maintenance of CD8+ T cells

Several previous studies outlined the importance of the histone H2A deubiquitinase MYSM1 in the regulation of stem cell quiescence and haematopoiesis. In this study we investigated the role of MYSM1 in T‐cell development. Using mouse models that allow conditional Mysm1 ablation at late stages of thymic development, we found that MYSM1 is intricately involved in the maintenance, activation and survival of CD8⁺ T cells. Mysm1 ablation resulted in a twofold reduction in CD8⁺ T‐cell numbers, and also led to a hyperactivated CD8⁺ T‐cell state accompanied by impaired proliferation and increased pro‐inflammatory cytokine production after ex vivo stimulation. These phenotypes coincided with an increased apoptosis and preferential up‐regulation of p53 tumour suppressor protein in CD8⁺ T cells. Lastly, we examined a model of experimental cerebral malaria, in which pathology is critically dependent on CD8⁺ T cells. In the mice conditionally deleted for Mysm1 in the T‐cell compartment, CD8⁺ T‐cell numbers remained reduced following infection, both in the periphery and in the brain, and the mice displayed improved survival after parasite challenge. Collectively, our data identify MYSM1 as a novel factor for CD8⁺ T cells in the immune system, increasing our understanding of the role of histone H2A deubiquitinases in cytotoxic T‐cell biology.     

The bronchopulmonary pathology of alpha-1 antitrypsin (AAT) deficiency: findings of the Death Review Committee of the national registry for individuals with Severe Deficiency of Alpha-1 Antitrypsin

To assess the pathological changes in the lungs and liver of 42 individuals who died while enrolled in the Registry of Individuals with Severe Deficiency of Alpha-1 Antitrypsin (AAT), all available histopathologic surgical or postmortem-derived specimens were reviewed by the pathologist member of the Death Review Committee. The underlying cause of death was emphysema in 34 patients and cirrhosis in 2 patients. Slides of lung were graded for emphysema, and liver specimens were graded for fibrosis, using respective pictorial scoring systems. Correlations between the degree of pathological abnormality and clinical features were evaluated. All lungs exhibited severe panacinar emphysema (mean emphysema score, 7.9 ± 1.06 [standard deviation], where 10 represents the greatest severity) with a lower lobe predominance. Centriacinar emphysema was minimal. No correlation was found between the pathological severity of emphysema and pulmonary function measurements, and no significant correlation was found between the degree of emphysema and the degree of hepatic fibrosis. Mildly increased bronchial gland-to-wall ratio accompanied mild inflammation and goblet cell hyperplasia. There were minimal changes in small airways. Dilatation of membranous bronchioles was a frequent finding; however, bronchiectasis of larger airways was a minor feature in only 6 patients (15%). Airway morphological features did not correlate with the clinical presence of chronic bronchitis or asthma. Although the lack of correlation between liver and lung pathological changes may reflect different pathogenetic mechanisms of liver disease and lung disease, the lack of correlation between emphysema grade and lung function likely reflects the skewed sample in a series of patients with advanced lung disease.     

A matter of timing: Early,not chronic phase intestinal nematode infection restrains control of a concurrent enteric protozoan infection

Infections with parasitic worms are often long lasting and associated with modulated immune responses. We analyzed the influence of the nematode Heligmosomoides polygyrus bakeri dwelling in the small intestine on concurrent protozoan infection with Eimeria falciformis residing in the cecum. To dissect the effects of a nematode infection in the early versus chronic phase, we infected animals with E. falciformis 6 or 28 days post H. p. bakeri infection. Only a concurrent early nematode infection led to an increased replication of the protozoan parasite, whereas a chronic worm infection had no influence on the control of E. falciformis. Increased protozoan replication correlated with the reduced production of IFN‐γ, IL‐12/23, CCL4, CXCL9 and CXCL10, reduced migration of T cells and increased expression of Foxp3 at the site of protozoan infection. This was accompanied by a stronger nematode‐specific Th2 response in gut‐draining LN. Protection of mice against challenge infections with the protozoan parasite was not altered. Hence, the detrimental effect of a nematode infection on the control of a concurrent protozoan infection is transient and occurs only in the narrow time window of the early phase of infection.