X-ray structure of the arenavirus glycoprotein GP2 in its postfusion hairpin conformation.
PNAS 108(50):19967 (2011)
Arenaviruses are important agents of zoonotic disease worldwide. The virions expose a tripartite envelope glycoprotein complex at their surface, formed by the glycoprotein subunits GP1, GP2 and the stable signal peptide. This complex is responsible for binding to target cells and for the subsequ...
A platelet-mediated system for shuttling blood-borne bacteria to CD8α+ dendritic cells depends on glycoprotein GPIb and complement C3.
Nature Immunology 12(12):1194 (2011)
The acquisition of pathogen-derived antigen by dendritic cells (DCs) is a key event in the generation of cytotoxic CD8(+) T cell responses. In mice, the intracellular bacterium Listeria monocytogenes is directed from the blood to splenic CD8α(+) DCs. We report that L. monocytogenes rapidly assoc...
Tissue macrophages suppress viral replication and prevent severe immunopathology in an interferon-I-dependent manner in mice.
Hepatology 52(1):25 (2010)
The innate immune response plays an essential role in the prevention of early viral dissemination. We used the lymphocytic choriomeningitis virus model system to analyze the role of tissue macrophages/Kupffer cells in this process. Our findings demonstrated that Kupffer cells are essential for t...
Long-lasting immunity by early infection of maternal-antibody-protected infants.
European Journal of Immunology 40(1):113 (2010)
Newborn higher vertebrates are largely immuno-incompetent and generally survive infections--including poxviruses--by maternal antibody protection. Here, we show that mice survived epidemics as adults only if exposed to lethal orthopoxvirus infections during infancy under the umbrella of maternal...
Innate immune-induced depletion of bone marrow neutrophils aggravates systemic bacterial infections.
PNAS 106(17):7107 (2009)
Neutrophils are the most abundant leukocytes in circulation and provide a primary innate immune defense function against bacterial pathogens before development of a specific immune response. These specialized phagocytes are short lived (12-24 hours) and continuously replenished from bone marrow....
Recombination of retrotransposon and exogenous RNA virus results in nonretroviral cDNA integration.
Science 323(5912):393 (2009)
Retroviruses have the potential to acquire host cell-derived genetic material during reverse transcription and can integrate into the genomes of larger, more complex DNA viruses. In contrast, RNA viruses were believed not to integrate into the host's genome under any circumstances. We found that...
Polyclonal and specific antibodies mediate protective immunity against enteric helminth infection.
Cell Host & Microbe 4(4):362 (2008)
Anti-helminth immunity involves CD4+ T cells, yet the precise effector mechanisms responsible for parasite killing or expulsion remain elusive. We now report an essential role for antibodies in mediating immunity against the enteric helminth Heligmosomoides polygyrus (Hp), a natural murine paras...
Aggravation of viral hepatitis by platelet-derived serotonin.
Nature Medicine 14(7):756 (2008)
More than 500 million people worldwide are persistently infected with hepatitis B virus or hepatitis C virus. Although both viruses are poorly cytopathic, persistence of either virus carries a risk of chronic liver inflammation, potentially resulting in liver steatosis, liver cirrhosis, end-stag...
Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors.
Journal of Experimental Medicine 205(1):53 (2008)
Many vaccination strategies and immune cell therapies aim at increasing the numbers of memory T cells reactive to protective antigens. However, the differentiation lineage and therefore the optimal generation conditions of CD4 memory cells remain controversial. Linear and divergent differentiati...
Long-term maternal imprinting of the specific B cell repertoire by maternal antibodies.
European Journal of Immunology 38(1):90 (2008)
Maternal antibodies protect newborns whilst they are immunologically immature. This study shows that maternal antibodies can also shape the B cell repertoire of the offspring long after the maternal antibodies themselves become undetectable. V(H)DJ(H) gene-targeted (VI10) mice expressing a heavy...
Extralymphatic virus sanctuaries as a consequence of potent T-cell activation.
Nature Medicine 13(11):1316 (2007)
T helper cells can support the functions of CD8(+) T cells against persistently infecting viruses such as murine lymphocytic choriomeningitis virus (LCMV), cytomegalovirus, hepatitis C virus and HIV. These viruses often resist complete elimination and remain detectable at sanctuary sites, such a...
Early antibodies specific for the neutralizing epitope on the receptor binding subunit of the lymphocytic choriomeningitis virus glycoprotein fail to neutralize the virus.
Journal of Virology 81(21):11650 (2007)
Lymphocytic choriomeningitis virus (LCMV) is a murine arenavirus whose glycoprotein consists of a transmembrane subunit (GP-2) and a receptor-binding subunit (GP-1). LCMV-neutralizing antibodies (nAbs) are directed against a single site on GP-1 and occur 1 month after the infection of cytotoxic-...
B cell activation state-governed formation of germinal centers following viral infection.
Journal of Immunology 179(9):5877 (2007)
Germinal centers are structures that promote humoral memory cell formation and affinity maturation, but the triggers for their development are not entirely clear. Activated extrafollicular B cells can form IgM-producing plasmablasts or enter a germinal center reaction and differentiate into memo...
MyD88 protects from lethal encephalitis during infection with vesicular stomatitis virus.
European Journal of Immunology 37(9):2434 (2007)
MyD88 is a key adaptor molecule in innate resistance, engaged in most Toll-like receptor, as well as IL-1 and IL-18, signalling. Here, we analyzed the role of MyD88 in innate resistance during infection with vesicular stomatitis virus (VSV) using myd88(-/-) mice. We found an increased susceptibi...
A lymphocytic choriomeningitis virus glycoprotein variant that is retained in the endoplasmic reticulum efficiently cross-primes CD8(+) T cell responses.
PNAS 104(33):13426 (2007)
Recent studies indicate that T cell cross-priming preferentially occurs against long-lived, stable proteins. We have studied cross-priming by using the glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV), a protein that normally is not MHC class I cross-presented. This study shows tha...
Identification and characterization of a novel antigen from the nematode Nippostrongylus brasiliensis recognized by specific IgE.
European Journal of Immunology 37(5):1275 (2007)
Identification and characterization of IgE-inducing antigens are important for elucidating the mechanisms involved in IgE-mediated immune responses in allergic diseases and parasite infections. While many allergens have been characterized, little is known about parasite antigens inducing specifi...
Dendritic cell-independent B cell activation during acute virus infection: a role for early CCR7-driven B-T helper cell collaboration.
Journal of Immunology 178(3):1468 (2007)
This study provides a detailed spatiotemporal interaction analysis between B cells, Th cells, and dendritic cells (DC) during the generation of protective antiviral B cell immunity. Following vesicular stomatitis virus (VSV) infection, conditional ablation of CD11c-positive DC at the time-point ...
"Negative vaccination" by specific CD4 T cell tolerisation enhances virus-specific protective antibody responses.
PLoS ONE 2(11):e1162 (2007)
Cooperation of CD4+ T helper cells with specific B cells is crucial for protective vaccination against pathogens by inducing long-lived neutralizing antibody responses. During infection with persistence-prone viruses, prolonged virus replication correlates with low neutralizing antibody response...
Parameters governing exhaustion of rare T cell-independent neutralizing IgM-producing B cells after LCMV infection.
European Journal of Immunology 36(12):3175 (2006)
The late appearance of neutralizing antibodies (nAb) against lymphocytic choriomeningitis virus (LCMV) has been attributed to various factors including immunopathology, low frequency of high-affinity specific B cells and competition by nonspecific polyclonal B cell activation. To investigate the...
Increased susceptibility to bacterial superinfection as a consequence of innate antiviral responses.
PNAS 103(42):15535 (2006)
The reason why severe localized or systemic virus infections enhance and aggravate bacterial superinfection is poorly understood. Here we show that virus-induced IFN type I caused apoptosis in bone marrow granulocytes, drastically reduced granulocyte infiltrates at the site of bacterial superinf...