Kristina Allers's research while affiliated with Charité Universitätsmedizin Berlin and other places

Publications (50)

Article
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Background & aims: Classical Whipple's disease (CWD) affects the gastrointestinal tract and causes chronic diarrhea, malabsorption, and barrier dysfunction with microbial translocation (MT). Immune reconstitution inflammatory syndrome (IRIS) is a serious complication during antimicrobial treatment of CWD. The pathomechanisms of IRIS have not been...
Article
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SARS-CoV-2 is a single-stranded RNA virus that causes coronavirus disease 2019 (COVID-19). Given its acute and often self-limiting course, components of the innate immune system are likely central in controlling virus replication thereby determining clinical outcome. Natural killer (NK) cells are innate lymphocytes with notable activity against a b...
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The SARS-CoV-2 pandemic has so far claimed over three and a half million lives worldwide. Though the SARS-CoV-2 mediated disease COVID-19 has first been characterized by an infection of the upper airways and the lung, recent evidence suggests a complex disease including gastrointestinal symptoms. Even if a direct viral tropism of intestinal cells h...
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The intesinal microbiome is considered important in human immunodeficiency virus (HIV) pathogenesis and therefore represents a potential therapeutic target to improve the patients’ health status. Longitudinal alterations in the colonic mucosa-associated microbiome during simian immunodeficiency virus (SIV) infection were investigated using a 16S rR...
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Hepatitis E virus (HEV) genotypes 3 and 4 (HEV-3, HEV-4) infections are an emerging public health issue in industrialized countries. HEV-3 and −4 are usually self-limiting but can progress to chronic hepatitis E in immunocompromised individuals. The molecular mechanisms involved in persistent infections are poorly understood. Micro RNAs (miRNAs) ca...
Article
Mucosal plasma cells (PC) and Ig production are essential to fend pathogens and to maintain mucosal homeostasis. In human Helicobacter pylori infection, mucosal PC express inducible NO synthase (iNOS), which positively correlates with clearance of experimental human infection. To characterize Ig genes and specificities of antral mucosal iNOS+ and i...
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Introduction: Chronic infection with Tropheryma whipplei, known as Whipple's disease (WD), classically affects the gastrointestinal tract, but any organ system may be affected, and isolated manifestations occur. Reliable diagnosis based on a combination of periodic acid-Schiff (PAS) staining, T. whipplei-specific immunohistochemistry (IHC), and po...
Article
Cell-free and cell-associated HIV may differently affect the immune system and the efficacy of prevention strategies. Here we examined mucosal events in SIV infection using infected cells together with cell-free virus versus cell-free virus alone. Intravenously inoculated SIV-infected cells disseminated the infection to the intestine within 16 hour...
Article
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Background: Classical Whipple's disease (CWD) is characterized by the lack of specific Th1 response towards Tropheryma (T.) whipplei in genetically predisposed individuals. The cofactor GrpE of heat-shock protein 70 (Hsp70) from T. whipplei was previously identified as B-cell antigen. We tested the capacity of Hsp70 and GrpE to elicit specific pro-...
Article
Classical Whipple’s disease (CWD) affects the gastrointestinal tract and rather elicits regulatory than inflammatory immune reactions. Mechanisms of malabsorption, diarrhea, and systemic immune activation are unknown. We here analyzed mucosal architecture, barrier function, and immune activation as potential diarrheal trigger in specimens from 52 C...
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CD8(+) T cells in the intestinal mucosa influence the HIV-associated pathogenesis, but little is known about the dynamics of mucosal CD8(+) T cell counts and activation of these cells during the course of infection. In this study, mucosal CD8(+) T cells in the duodenum were studied at different stages of HIV infection, starting from the seronegativ...
Article
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The mucosal immune system is relevant for homeostasis, immunity, and also pathological conditions in the gastrointestinal tract. Inducible NO synthase (iNOS)-dependent production of NO is one of the factors linked to both antimicrobial immunity and pathological conditions. Upregulation of iNOS has been observed in human Helicobacter pylori infectio...
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Clinical manifestations of leptospirosis are highly variable: from asymptomatic to severe and potentially fatal. The outcome of the disease is usually determined in the immunological phase, beginning in the second week of symptoms. The underlying mechanisms, predictive factors, and individual immune responses that contribute to clinical variations...
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Whether and to what extent gut mucosal CD4(+) T cells of HIV-infected patients can be restored by combination antiretroviral therapy (cART) is not yet fully resolved. We studied absolute numbers, differentiation, and activation of mucosal CD4(+) T cells at different stages of HIV infection and assessed the effect of timing of cART initiation on thi...
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Accumulation of Tropheryma whipplei-stuffed macrophages in the duodenum, impaired T. whipplei-specific Th1 responses, and weak secretion of interleukin-12 (IL-12) are hallmarks of classical Whipple's disease (CWD). This study addresses dendritic cell (DC) functionality during CWD. We documented composition, distribution, and functionality of DC ex...
Article
Knowledge about HIV infection in older persons is becoming increasingly important. CD4 T cells are essential for protective immunity, but little is known about the effect of age on the CD4 T cell impairment in HIV infection. Treatment-naïve patients aged older than 50 or younger than 40 years were studied for absolute and relative frequencies of CD...
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Background: Mucosal macrophages are involved in the maintenance of epithelial barrier integrity and the elimination of invading pathogens. Although an intestinal barrier defect and microbial translocation are hallmarks of human immunodeficiency virus (HIV) infection, recent data on gut mucosal macrophages in HIV infection are sparse. Methods: Tr...
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Bacterial vectors have been proposed as novel vaccine strategies to induce strong cellular immunity. Attenuated strains of Brucella abortus comprise promising vector candidates since they have the potential to induce strong CD4(+) and CD8(+) T-cell mediated immune responses in the absence of excessive inflammation as observed with other Gram-negati...
Data
Expression of DC maturation markers by DCs incubated with heat-inactivated B. abortus strain S19. Immature DCs were incubated in the presence of heat-inactivated B. abortus S19 (equivalent to MOI 10) or kept in GM-CSF and IL-4 as immature cells. After 48 h, the phenotype of the cells was characterized by flow cytometry. Medians of the MFIs as well...
Data
Expression of DC maturation markers by B. abortus S19-infected DCs. Monocyte-derived immature DCs were infected with B. abortus S19 (MOI, 20) for 1 h, the bacteria were washed out, and the cells were incubated for another 48 h. Control cells were left uninfected. After 48 h, the phenotype of the cells was determined by flow cytometry. Medians of th...
Data
Expression of DC maturation markers by DCs upon infection with B. abortus S19 and cultured in the presence of pro-inflammatory cytokines. Monocyte-derived immature DCs were infected with B. abortus S19 (MOI, 20) for 1 h, the bacteria were washed out, and the cells incubated in the presence of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, PGE2). U...
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Background: Macrophage heterogeneity reflects their plasticity in response to environmental stimuli. Usually human macrophages are characterized by analysis of surface molecules or cytokine expression while functional assays are established in the mouse system but lacking for various human specimens. Methods: To evaluate the value of analysis of...
Article
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During antimicrobial treatment of classic Whipple's disease (CWD), the chronic systemic infection with Tropheryma whipplei, immune reconstitution inflammatory syndrome (IRIS), is a serious complication. The aim of our study was to characterize the immunological processes underlying IRIS in CWD. Following the definition of IRIS, we describe histolog...
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In this paper, we identify mechanisms of watery diarrhea in microscopic colitis (MC). Biopsies from the sigmoid colon of patients with collagenous colitis and treated lymphocytic colitis were analyzed in miniaturized Ussing chambers for electrogenic sodium transport and barrier function with one-path impedance spectroscopy. Cytometric bead arrays (...
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Helicobacter pylori blocks the proliferation of human CD4+ T cells, facilitated by vacuolating exotoxin (VacA) and γ-glutamyl transpeptidase (GGT). H. pylori–triggered T-cell reactions in mice correlate with bacterial cholesterol and cholesterol α-glucoside content but their role in human cells is unclear. We characterized the effect of VacA, GGT,...
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Classical Whipple's disease (CWD) is caused by chronic infection with Tropheryma whipplei that seems to be associated with an underlying immune defect. The pathognomonic hallmark of CWD is a massive infiltration of the duodenal mucosa with T. whipplei-infected macrophages that disperse systemically to many other organ systems. An alleviated inflamm...
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HIV entry into CD4(+) cells requires interaction with a cellular receptor, generally either CCR5 or CXCR4. We have previously reported the case of an HIV-infected patient in whom viral replication remained absent despite discontinuation of antiretroviral therapy after transplantation with CCR5Δ32/Δ32 stem cells. However, it was expected that the lo...
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Whipple disease, which is caused by infection with Tropheryma whipplei, can be treated effectively with antimicrobials. Occasionally, inflammation reappears after initial improvement; this is often interpreted as refractory or recurrent disease. However, polymerase chain reaction for T. whipplei in tissue is sometimes negative during reinflammation...
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Whipple's disease is a chronic multisystemic infection caused by Tropheryma whipplei that is characterized by arthritis, weight loss, and diarrhea. The immunological defects in the duodenal mucosa, the site of major replication of the agent underlying the pathogenesis of Whipple's disease, are poorly understood. Mucosal immunoglobulins are essentia...
Article
A barrier defect of the intestinal mucosa is thought to affect the progression of human immunodeficiency virus (HIV) infection. It is not clear whether the mucosal barrier impairment already is present in acute infection and what mechanisms cause this defect. We analyzed T-cell subsets, epithelial apoptosis, and barrier function of the duodenal muc...
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The gastrointestinal tract represents a major site for human and simian immunodeficiency virus (HIV and SIV) replication and CD4+ T-cell depletion. Despite severe depletion of mucosal CD4+ T cells, FOXP3+ regulatory CD4+ T cells (Treg) are highly increased in the gut mucosa of chronically HIV-infected individuals and may contribute to HIV pathogene...
Article
Whipple's disease is a chronic multisystemic infection caused by Tropheryma whipplei. Host factors likely predispose for the establishment of an infection, and macrophages seem to be involved in the pathogenesis of Whipple's disease. However, macrophage activation in Whipple's disease has not been studied systematically so far. Samples from 145 Whi...
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Infection with the human immunodeficiency virus type 1 (HIV-1) requires the presence of a CD4 receptor and a chemokine receptor, principally chemokine receptor 5 (CCR5). Homozygosity for a 32-bp deletion in the CCR5 allele provides resistance against HIV-1 acquisition. We transplanted stem cells from a donor who was homozygous for CCR5 delta32 in a...
Article
In studying immune responses towards the poliovirus, data about T cell mediated immunity in the intestine as the main portal of viral entry in disease and vaccination is lacking. We treated two macaques with oral Polio vaccine and collected duodenal and colonic biopsy specimens. RNA isolation, reverse transcription, and polymerase chain reaction we...
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Impairment of the gastrointestinal mucosal barrier contributes to progression of HIV infection. The purpose of this study was to investigate the effect of highly active antiretroviral therapy (HAART) on the HIV-induced intestinal barrier defect and to identify underlying mechanisms. Epithelial barrier function was characterised by impedance spectro...
Article
Adoptive cell transfer may be a successful strategy in anticancer therapy and its therapeutic efficiency depends on the access of transferred cells to the tumor site and their persistence in vivo. Nevertheless, the migration properties of autologous in vitro-activated T cells in primates are largely unknown. Here, we established the long-term track...
Article
The establishment of persistent infection is one of the major obstacles facing the eradication of HIV-1. To improve our understanding of the mechanisms of viral persistence, we investigated the fate of defined viral quasispecies under conditions that might favor their eradication. We retrospectively analyzed changes in viral populations in HIV-1-in...
Article
Efficient antiretroviral therapy (ART) of HIV-1 infection reduces the viral load to undetectable levels and restores the immune system. However, therapy failure appears in a substantial fraction of patients and is mostly associated with the appearance of drug-resistant viruses. It is still not clear when the drug pressure leads to the earliest sele...
Article
RNA interference is a powerful tool used to inhibit human immunodeficiency virus type 1 (HIV-1) replication in vitro. Almost all HIV-1 genes have been targets for small interfering RNA (siRNA) molecules, and HIV-1 replication can be specifically and successfully inhibited by this technique. RNA interference has been proposed as an alternative strat...
Article
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The use of structured treatment interruption (STI) in human immunodeficiency virus (HIV)–infected subjects is currently being studied as an alternative therapeutic strategy for HIV-1. The potential risk for selection of drug-resistant HIV-1 variants during STI is unknown and remains a concern. Therefore, the emergence of drug resistance in sequenti...

Citations

... Hence, SARS-CoV-2 infection may impair antiviral immunity in a time-dependent manner, leading to depleted immune cells that are dysfunctional against the virus [71,72]. In both cytotoxic lymphocytes and NK cells of patients with COVID-19 disease, the expression of NKG2A has upregulated as well as expression of IFN-γ, CD107a, granzyme B, and IL-2 is downregulated; this event is consistent with functional exhaustion and disease progression [73][74][75]. ...
... Another important factor of the intestinal mechanical barrier integrity is enterocytes' apoptosis. A previous immunohistochemical study in COVID-19 patients detected significantly increased numbers of cleaved caspase-3(+) apoptotic epithelial cells [49]. Highly proliferating epithelial cells were also seen indicating a regenerative response to intestinal injury. ...
... This contributed to the observed decrease in the ratio of Firmicutes to Bacteroidetes, in contrast to reports in HIV infection [49,50]. A similar early decrease in F/B ratio, which was progressive and significant during chronic untreated infection, has been reported earlier in the colonic mucosal microbiome [51] and fecal microbiome [29] of SIV-infected rhesus macaques, suggesting that an early decrease in several species of Firmicutes and increase in Bacteroidetes may be specific to nonhuman primates or may have been missed in cross-sectional human studies. The gut microbiota changes following HIV/SIV infection are linked to disruption of the gut epithelial barrier, bacterial translocation of intestinal products from the lumen into the lamina propria, and inflammation [25,43,52,53]. ...
... Notably, a recent in vitro study has shown a similar effect of miR-122-3p on HEV replication [81]. Another microRNA, miR-99a-5p, shown to modulate HBV replication by promoting IGF-1R/PI3K/Akt/mTOR/ULK1 signaling-induced autophagy, has been found to be upregulated in acute and chronic HEV patients [82]. ...
... Von den 20 bestätigten MW-Patienten waren 16 Patienten therapienaïv und 4 Patienten wurden zuvor für < 14 Tage anbehandelt. Nachgedruckt und übersetzt mit Genehmigung von Molecular Diagnosis & Therapy[175]. ...
... Human and Simian Immunodeficiency Virus (HIV, SIV) infections are associated with dramatic changes in mucosal tissues such as the gastrointestinal tract (GIT) with massive replication and depletion of CD4 T cells during the acute stages of infection (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Viral replication and associated inflammation persists in these tissues over the course of infection that is accompanied by damage to intestinal epithelial barrier, translocation of microbial products, immune activation and progressive loss of CD4 T cells (18)(19)(20)(21)(22). Though peripheral tissues experience significant levels of restoration after antiretroviral therapy, viral replication in mucosal tissues continues to persist with incomplete restoration of the immune system to a homeostatic state (23-38). ...
... Thus, increased homing of pro-inflammatory lymphocytes to enthesial tissue via the α4β1-VCAM-1 axis in response to α4β7 blockade might trigger inflammation. A similar process has already been suggested to promote extraintestinal manifestations of Crohn's disease in the lung [11]. Regarding the rather slow onset of action of vedolizumab in reducing the inflammatory burden in IBD, such alterations in cell trafficking pathways might be better reconcilable with the observed timelines of enthesitis development. ...
... The nearby generation of provocative cytokines through macrophages and endothelial cells within the fringe might actuate lymphocyte invasion through a defective endothelial obstruction taken after by central aggravation, indeed in immunologically ensured tissues such as joints or the neuronal domain (Schneider et al. 2008).Currently hydroxychloroquine (600 mg/day) and doxycycline (200 mg/day) used for treatment of whipple's disease for 12-18 months, but life time follow up is required (Lagier et al. 2014), so it is time consuming treatment process and only few handful trials were conducted in earlier studies (Feurle et al. 2013). Nowadays epitope based vaccines provide better options in search of good treatment strategy for such type of harmful and rare malady, even if the individuals are genetically predisposed as in case of classical Whipple's disease (Trotta et al. 2017). This modern approach of putative vaccine determination which involves the use of proteomic databases is very handy and easy to use method not only for rare bacterial pathogens, but also very effective in case of harmful viruses like Nipah (Kaushik 2019). ...
... Gastrointestinal symptoms in this disease, such as chronic diarrhea and malabsorption, clearly indicate a dysfunction of the small intestinal mucosa. 1,2 During antimicrobial treatment, up to 10% of CWD patients are affected by immune reconstitution inflammatory syndrome (IRIS). 3 The occurrence of IRIS CWD is associated with a rapid and severe clinical deterioration that results in significant morbidity and mortality. ...
... The duodenum is a major site where HIV-associated immune cell disruption is markedly increased and is a major site of HIV persistence during suppressive ART (23,24). Here, we investigated why the duodenum remains a major reservoir of HIV during suppressive ART despite harboring abundant resident CD8 + T cells. ...