Apmis

ULVESTAD, ELLING; THOMSEN, ALLAN RANDRUP

doi: 10.1111/j.1600-0463.2009.02455.xpmid: 19400858

ULVESTAD, ELLING

doi: 10.1111/j.1600-0463.2009.02457.xpmid: 19400859

Hosts and microbes associate in a variety of relations along a continuum ranging from symbiotic to pathogenic. Defence mechanisms have been evolutionarily selected in both hosts and microbes to protect the organism's integrity. Such defences have to be utilized with caution. They must be adapted to the tasks at hand; otherwise any symbiotic relation would be impossible. To explain this cautionary use of defences we need to understand how life on Earth evolved into cooperative and competing entities at various levels of organization. The purpose of this article is to review theory and selected mechanisms relating to the evolution and development of host–microbe interactions, with special emphasis on host responses. The rationale is that without theory, extrapolations from misleading observations can dominate and distort, for a significant time, the course of a scientific field. The argument is set forth that social evolution theory provides a conceptual framework for addressing questions relating to interaction between hosts and microbes. The article is a partial summary of arguments presented in my book Defending life – the nature of host–parasite relations.

RASMUSSEN, SIMON B.; REINERT, LINE S.; PALUDAN, SØREN R.

doi: 10.1111/j.1600-0463.2009.02456.xpmid: 19400860

The innate immune system constitutes the first line of defense against infections and is also important for initiating the development of an adaptive immune response. The innate immune system recognizes microbial infection through germline‐encoded pattern recognition receptors, which are responsible for decoding the microbial fingerprint and activating an appropriate response against the invading pathogen. In this review, we present and discuss current knowledge on how the innate immune system recognizes intracellular pathogens, activates intracellular signaling, induces gene expression, and orchestrates the microbicidal response against pathogens with a habitat within host cells.

CHRISTENSEN, JEANETTE ERBO; THOMSEN, ALLAN RANDRUP

doi: 10.1111/j.1600-0463.2009.02451.xpmid: 19400861

The host counters a viral infection through a complex response made up of components belonging to both the innate and the adaptive immune system. In this report, we review the mechanisms underlying this response, how it is induced and how it is co‐ordinated. As cell–cell communication represents the very essence of immune system physiology, a key to a rapid, efficient and optimally regulated immune response is the ability of the involved cells to rapidly shift between a stationary and a mobile state, combined with stringent regulation of cell migration during the mobile state. Through the co‐ordinated recruitment of different cell types intended to work in concert, cellular co‐operation is optimized particularly under conditions that may involve rare cells. Consequently, a major focus is placed on presenting an overview of the co‐operative events and the associated cell migration, which is essential in mounting an efficient host response and co‐ordinating innate and adaptive immunity during a primary viral infection.

WIESEL, MELANIE; WALTON, SENTA; RICHTER, KIRSTEN; OXENIUS, ANNETTE

doi: 10.1111/j.1600-0463.2009.02459.xpmid: 19400862

CD8 T cells are pivotal for the control of many intracellular pathogens, and besides their role in immediate control of infections, CD8 T cells have the capacity to differentiate into long‐lived antigen‐independent memory CD8 T cells, at least in situations of acute and resolved infections. The population of memory cells is heterogeneous with respect to their phenotype, their anatomical localization and their functional capacities in order to afford optimal protection against secondary infections. In the past years, it has become clear that multiple in vivo parameters are involved in shaping the composition of the memory CD8 T cell population, including antigen load, duration and strength of CD8 T cell stimulation, the level of inflammation, availability of CD4 T cell help and CD8 T cell precursor frequencies. With respect to the timing when CD8 T cells are committed to become memory cells, several models have been proposed. In contrast to acute, resolved infection, the continued in vivo exposure to high levels of antigen during persistent chronic viral infection precludes the development of long‐lived antigen‐independent memory CD8 T cells and might even result in severe dysfunction of virus‐specific CD8 T cells.

KALLAND, KARL‐HENNING; KE, XI‐SONG; ØYAN, ANNE MARGRETE

doi: 10.1111/j.1600-0463.2009.02452.xpmid: 19400863

Viruses enter host cells in order to complete their life cycles and have evolved to exploit host cell structures, regulatory factors and mechanisms. The virus and host cell interactions have consequences at multiple levels, spanning from evolution through disease to models and tools for scientific discovery and treatment. Virus‐induced human cancers arise after a long duration of time and are monoclonal or oligoclonal in origin. Cancer is therefore a side effect rather than an essential part of viral infections in humans. Still, 15–20% of all human cancers are caused by viruses. A review of tumour virology shows its close integration in cancer research. Viral tools and experimental models have been indispensible for the progress of molecular biology. In particular, retroviruses and DNA tumour viruses have played major roles in our present understanding of the molecular biology of both viruses and the host. Recently, additional complex relationships due to virus and host co‐evolution have appeared and may lead to a further understanding of the overall regulation of gene expression programmes in cancer.

WILLIAMS, KENNETH C.; BURDO, TRICIA H.

doi: 10.1111/j.1600-0463.2009.02450.xpmid: 19400864

The human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) have a long biological history. Both viruses evolved from Africa and remnants of them can be found in the ‘fossil record’ of several species in which they are not endemic. SIV remains endemic in several species of monkeys in Africa where it does not cause immune deficiency. HIV and SIV actively replicate within humans and Asian non‐human primates, despite cellular and genetic viral restriction factors and genes, and at times robust innate and adaptive immune responses. While Lentiviruses are considered ‘slow viruses’ it is clear in humans and susceptible Asian monkeys that virus production is rapid and highly active. This results in a massive loss of CD4+ memory effector T cells early after infection and a continued race between viral evolution, cytotoxic lymphocytes, and failed neutralizing antibody responses. Concurrently, HIV and SIV can infect monocyte/macrophage populations in blood and more importantly in tissues, including the central nervous system, where the virus can remain sequestered and not cleared by anti‐retroviral therapy, and hide for years. This review will discuss species and cellular barriers to infection, and the role of innate and acquired immunity with infection and pathogenesis of HIV and SIV in select species.

RÖLLE, ALEXANDER; OLWEUS, JOHANNA

doi: 10.1111/j.1600-0463.2009.02449.xpmid: 19400865

Human cytomegalovirus (HCMV) is a β‐herpesvirus that infects the majority of the population during early childhood and thereafter establishes life‐long latency. Primary infection as well as spontaneous reactivation usually remains asymptomatic in healthy hosts but can, in the context of systemic immunosuppression, result in substantial morbidity and mortality. HCMV counteracts the host immune response by interfering with the recognition of infected cells. A growing body of literature has also suggested that the virus evades the immune system by paralyzing the initiators of antiviral immune responses – the dendritic cells (DCs). In the current review, we discuss the effects of CMV (HCMV and murine CMV) on various DC subsets and the ensuing innate and adaptive immune responses. The impact of HCMV on DCs has mainly been investigated using monocyte‐derived DCs, which are rendered functionally impaired by infection. In mouse models, DCs are targets of viral evasion as well, but the complex cross‐talk between DCs and natural killer cells has, however, demonstrated an instrumental role for DCs in the control and clearance of viral infection. Fewer studies address the role of peripheral blood DC subsets, plasmacytoid DCs and CD11c+ myeloid DCs in the response against HCMV. These DCs, rather than being paralyzed by HCMV, are largely resistant to infection, mount a vigorous first‐line defense and induce T‐cell responses to the virus. This possibly provides a partial explanation for an intriguing conundrum: the highly efficient control of viral infection and reactivation in immunocompetent hosts in spite of multi‐layered viral evasion mechanisms.

MYRMEL, HELGE; ULVESTAD, ELLING; ÅSJØ, BIRGITTA

doi: 10.1111/j.1600-0463.2009.02454.xpmid: 19400866

Hepatitis C virus (HCV) has a high propensity to establish chronic infection with end‐stage liver disease. The high turnover of virus particles and high transcription error rates due to lack of proof‐reading function of the viral polymerase imply that HCV exists as quasispecies, thus enabling the virus to evade the host immune response. Clearance of the virus is characterized by a multispecific, vigorous and persistent T‐cell response, whereas T‐cell responses are weak, narrow and transient in patients who develop chronic infection. At present, standard treatment is a combination of pegylated interferon‐α and ribavirin, with a sustained viral response rate of 40–80%, depending on genotype. The mechanisms for the observed synergistic effects of the two drugs are still not known in detail, but in addition to direct antiviral mechanisms, the immunomodulatory effects of both drugs seem to be important, with a shift from Th2‐ to Th1‐cytokine profiles in successfully treated patients. This article describes virus–host relations in the natural course of HCV infection and during treatment.

DIETRICH, JES; DOHERTY, T. MARK

doi: 10.1111/j.1600-0463.2009.02458.xpmid: 19400867

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), remains a major worldwide health problem that causes more than 2 million deaths annually. In addition, an estimated 2 billion people are latently infected with M. tuberculosis. The bacterium is one of the oldest human pathogens and has evolved complex strategies for survival. Therefore, to be successful in the high endemic regions, any future TB vaccine strategy will have to be tailored in accordance with the resulting complexity of the TB infection and anti‐mycobacterial immune response. In this review, we will discuss what is presently known about the interaction of M. tuberculosis with the immune system, and how this knowledge is used in new and more advanced vaccine strategies.