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Author

Clas Ahlm

Other affiliations: Karolinska University Hospital
Bio: Clas Ahlm is an academic researcher from Umeå University. The author has contributed to research in topics: Hantavirus & Puumala virus. The author has an hindex of 37, co-authored 152 publications receiving 4481 citations. Previous affiliations of Clas Ahlm include Karolinska University Hospital.


Papers
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Journal ArticleDOI
TL;DR: This work has shown that acute hantavirus infection in humans triggers a rapid expansion and long-term persistence of NK cells, which in turn influences the ability of these cells to reprogram and reprogram themselves for use in wound healing.
Abstract: Natural killer (NK) cells are known to mount a rapid response to several virus infections. In experimental models of acute viral infection, this response has been characterized by prompt NK cell activation and expansion followed by rapid contraction. In contrast to experimental model systems, much less is known about NK cell responses to acute viral infections in humans. We demonstrate that NK cells can rapidly expand and persist at highly elevated levels for >60 d after human hantavirus infection. A large part of the expanding NK cells expressed the activating receptor NKG2C and were functional in terms of expressing a licensing inhibitory killer cell immunoglobulin-like receptor (KIR) and ability to respond to target cell stimulation. These results demonstrate that NK cells can expand and remain elevated in numbers for a prolonged period of time in humans after a virus infection. In time, this response extends far beyond what is considered normal for an innate immune response.

449 citations

Journal ArticleDOI
TL;DR: Serum Levels of the two soluble TNF receptors p55 and p75 correlated with levels of the cytokine, indicating that receptor binding may be the reason for lack of bioactivity in vitro.
Abstract: Plasma levels of cytokines were measured by EIA in 15 subjects hospitalized with nephropathia epidemica, a European form of hantavirus-induced hemorrhagic fever with renal syndrome. Concentrations of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 were increased in all patients at admission, and the concentration of IL-10 was increased in most. TNF-alpha concentrations were still increased 1 week after onset of disease; levels of IL-6 and IL-10 were normalized. TNF-alpha was undetectable by the WEHI cell assay in serum samples obtained throughout the acute phase of disease. Serum levels of the two soluble TNF receptors p55 and p75 correlated with levels of the cytokine, indicating that receptor binding may be the reason for lack of bioactivity in vitro. TNF-alpha is known to induce pathophysiologic and clinical changes similar to those seen in nephropathia epidemica and in diseases caused by other hantaviruses.

173 citations

Journal ArticleDOI
TL;DR: The RVF outbreak in Sudan emphasizes the need for collaboration between veterinary and health authorities, entomologists, environmental specialists, and biologists, as the best strategy towards the prevention and control of RVF.
Abstract: Rift Valley fever (RVF) is a neglected, emerging, mosquito-borne disease with severe negative impact on human and animal health and economy. RVF is caused by RVF virus (RVFV) affecting humans and a wide range of animals. The virus is transmitted through bites from mosquitoes and exposure to viremic blood, body fluids, or tissues of infected animals. During 2007 a large RVF outbreak occurred in Sudan with a total of 747 confirmed human cases including 230 deaths (case fatality 30.8%); although it has been estimated 75,000 were infected. It was most severe in White Nile, El Gezira, and Sennar states near to the White Nile and the Blue Nile Rivers. Notably, RVF was not demonstrated in livestock until after the human cases appeared and unfortunately, there are no records or reports of the number of affected animals or deaths. Ideally, animals should serve as sentinels to prevent loss of human life, but the situation here was reversed. Animal contact seemed to be the most dominant risk factor followed by animal products and mosquito bites. The Sudan outbreak followed an unusually heavy rainfall in the country with severe flooding and previous studies on RVF in Sudan suggest that RVFV is endemic in parts of Sudan. An RVF outbreak results in human disease, but also large economic loss with an impact beyond the immediate influence on the directly affected agricultural producers. The outbreak emphasizes the need for collaboration between veterinary and health authorities, entomologists, environmental specialists, and biologists, as the best strategy towards the prevention and control of RVF.

131 citations

Journal ArticleDOI
TL;DR: The chance of infection in bank voles captured in a region in northern Sweden endemic for hantavirus was greatest during the peak of the population cycle, implying that the likelihood of exposure to hantvirus increases with increasing population density.
Abstract: The bank vole (Clethrionomys glareolus) is the natural reservoir of Puumala virus (PUUV), a species in the genus Hantavirus. PUUV is the etiologic agent of nephropathia epidemica, a mild form of hemorrhagic fever with renal syndrome. Factors that influence hantavirus transmission within host populations are not well understood. We evaluated a number of factors influencing on the association of increased PUUV infection in bank voles captured in a region in northern Sweden endemic for the virus. Logistic regression showed four factors that together correctly predicted 80% of the model outcome: age, body mass index, population phase during sampling (increase, peak, or decline/low), and gender. This analysis highlights the importance of population demography in the successful circulation of hantavirus. The chance of infection was greatest during the peak of the population cycle, implying that the likelihood of exposure to hantavirus increases with increasing population density.

123 citations

Journal ArticleDOI
TL;DR: Heterologous vaccination with ChAdOx1 nCoV-19 and mRNA-1273 Health care workers who had received a dose of ChAdox1 n CoV19 were offered a choice of receiving either ChAd Ox 1 nCov-19 or mRNA -1273 9 t
Abstract: Heterologous Vaccination with ChAdOx1 nCoV-19 and mRNA-1273 Health care workers who had received a dose of ChAdOx1 nCoV-19 were offered a choice of receiving either ChAdOx1 nCoV-19 or mRNA-1273 9 t...

123 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
TL;DR: Findings that have advanced the understanding of IL-10 and its receptor are highlighted, as well as its in vivo function in health and disease.
Abstract: Interleukin-10 (IL-10), first recognized for its ability to inhibit activation and effector function of T cells, monocytes, and macrophages, is a multifunctional cytokine with diverse effects on most hemopoietic cell types. The principal routine function of IL-10 appears to be to limit and ultimately terminate inflammatory responses. In addition to these activities, IL-10 regulates growth and/or differentiation of B cells, NK cells, cytotoxic and helper T cells, mast cells, granulocytes, dendritic cells, keratinocytes, and endothelial cells. IL-10 plays a key role in differentiation and function of a newly appreciated type of T cell, the T regulatory cell, which may figure prominently in control of immune responses and tolerance in vivo. Uniquely among hemopoietic cytokines, IL-10 has closely related homologs in several virus genomes, which testify to its crucial role in regulating immune and inflammatory responses. This review highlights findings that have advanced our understanding of IL-10 and its receptor, as well as its in vivo function in health and disease.

6,308 citations

Journal ArticleDOI
TL;DR: Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas.
Abstract: Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.

2,109 citations

Journal ArticleDOI
05 Feb 2021-Science
TL;DR: This article analyzed multiple compartments of circulating immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months after infection.
Abstract: Understanding immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for improving diagnostics and vaccines and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥6 months after infection. Immunoglobulin G (IgG) to the spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month after symptom onset. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3 to 5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.

1,980 citations

BookDOI
01 Jan 2011
TL;DR: Firm evidence is provided for Foxp3+CD25+CD4+ Treg cells as an indispensable cellular constituent of the normal immune system for establishing and maintaining immunologic self-tolerance and immune homeostasis.
Abstract: Despite the skepticism that once prevailed among immunologists, it is now widely accepted that the normal immune system harbors a T-cell population, called regulatory T cells (Treg cells), specialized for immune suppression. It was first shown that depletion of a T-cell subpopulation from normal rodents produced autoimmune disease. Search for a molecular marker specific for such autoimmune-preventive Treg cells has revealed that the majority, if not all, of them constitutively express the CD25 molecule as depletion of CD25+CD4+ T cells spontaneously evokes autoimmune disease in otherwise normal rodents. The expression of CD25 by Treg cells has made it possible to delineate their developmental pathways, in particular their thymic development, and establish simple in vitro assay for assessing their suppressive activity. The marker and the in vitro assay have helped to identify human Treg cells with similar functional and phenotypic characteristics. Recent efforts have shown that natural Treg cells specifically express the transcription factor Foxp3 and that mutations of the Foxp3 gene produce a variety of immunological diseases in humans and rodents. Specific expression of Foxp3 in natural Treg cells has enabled their functional and developmental characterization by genetic approach. These studies altogether have provided firm evidence for Foxp3+CD25+CD4+ Treg cells as an indispensable cellular constituent of the normal immune system for establishing and maintaining immunologic self-tolerance and immune homeostasis. Treg cells are now within the scope of clinical use to treat immunological diseases and control physiological and pathological immune responses.

1,745 citations