CTLA-4 control over Foxp3+ regulatory T cell function

Naturally occurring Foxp3+CD4+ regulatory T cells (Tregs) are essential for maintaining immunological self-tolerance and immune homeostasis. Here, we show that a specific deficiency of cytotoxic T lymphocyte antigen 4 (CTLA-4) in Tregs results in spontaneous development of systemic lymphoproliferation, fatal T cell-mediated autoimmune disease, and hyperproduction of immunoglobulin E in mice, and it also produces potent tumor immunity. Treg-specific CTLA-4 deficiency impairs in vivo and in vitro suppressive function of Tregs-in particular, Treg-mediated down-regulation of CD80 and CD86 expression on dendritic cells. Thus, natural Tregs may critically require CTLA-4 to suppress immune responses by affecting the potency of antigen-presenting cells to activate other T cells.     

A haptoglobin-hemoglobin receptor conveys innate immunity to Trypanosoma brucei in humans

The protozoan parasite Trypanosoma brucei is lysed by apolipoprotein L-I, a component of human high-density lipoprotein (HDL) particles that are also characterized by the presence of haptoglobin-related protein. We report that this process is mediated by a parasite glycoprotein receptor, which binds the haptoglobin-hemoglobin complex with high affinity for the uptake and incorporation of heme into intracellular hemoproteins. In mice, this receptor was required for optimal parasite growth and the resistance of parasites to the oxidative burst by host macrophages. In humans, the trypanosome receptor also recognized the complex between hemoglobin and haptoglobin-related protein, which explains its ability to capture trypanolytic HDLs. Thus, in humans the presence of haptoglobin-related protein has diverted the function of the trypanosome haptoglobin-hemoglobin receptor to elicit innate host immunity against the parasite.     

The bST debate: The relationship between awareness and acceptance of technological advances

Despite concerns of consumer protection andenvironmental groups that the use of geneticallyproduced growth hormone in milk-producing cows mayadversely impact the safety of the milk supply,scientific evidence and governmental findings from theUSA appear to indicate that milk fromtreated cows is identical in quality, taste, andnutritional value to milk from untreated cows. Limitedexperience to date in the USA demonstrateslittle consumer resistance to milk from cows that havereceived the growth hormone, which can lead to a 15%increase in milk production. In fact, if there is noperceived differentiation between the two forms ofmilk, the issue offers little choice to consumers atlarge, and may result in economic benefit only toselected dairy farmers, as well as the producers ofthe genetically produced growth hormone. Thissituation in the USA may be an example ofdysfunctional technology transfer, with desirablebenefits to a few, and as yet unknown benefits to thesociety. The USA has taken a bold move inapproving the use of bovine growth hormone in milk-producing cows, while the European Union has takena divergent approach by enacting lengthy moratoriumsagainst its use. The basic lesson to be learned fromthe bST case is that lack of awareness amonggovernment officials and the public at large serves asa significant impediment to the adoption of newtechnologies. Accordingly, delays may occur indelivery of significant social benefits to thepopulation as a whole. Obviously, the issue extendsbeyond bST.     

Sex matters in meiosis

In mammals, fertilization typically involves the ovulation of one or a few eggs at one end of the female reproductive tract and the entry of millions of sperm at the other. Given this disparity in numbers, it might be expected that the more precious commodity-eggs-would be subject to more stringent quality-control mechanisms. However, information from engineered mutations of meiotic genes suggests just the opposite. Specifically, the available mutants demonstrate striking sexual dimorphism in response to meiotic disruption; for example, faced with adversity, male meiosis grinds to a halt, whereas female meiosis soldiers on. This female "robustness" comes with a cost, however, because aneuploidy appears to be increased in the resultant oocytes.     

Differences between tight and loose cultures: a 33-nation study

With data from 33 nations, we illustrate the differences between cultures that are tight (have many strong norms and a low tolerance of deviant behavior) versus loose (have weak social norms and a high tolerance of deviant behavior). Tightness-looseness is part of a complex, loosely integrated multilevel system that comprises distal ecological and historical threats (e.g., high population density, resource scarcity, a history of territorial conflict, and disease and environmental threats), broad versus narrow socialization in societal institutions (e.g., autocracy, media regulations), the strength of everyday recurring situations, and micro-level psychological affordances (e.g., prevention self-guides, high regulatory strength, need for structure). This research advances knowledge that can foster cross-cultural understanding in a world of increasing global interdependence and has implications for modeling cultural change.     

Different B cell populations mediate early and late memory during an endogenous immune response

Memory B cells formed in response to microbial antigens provide immunity to later infections; however, the inability to detect rare endogenous antigen-specific cells limits current understanding of this process. Using an antigen-based technique to enrich these cells, we found that immunization with a model protein generated B memory cells that expressed isotype-switched immunoglobulins (swIg) or retained IgM. The more numerous IgM(+) cells were longer lived than the swIg(+) cells. However, swIg(+) memory cells dominated the secondary response because of the capacity to become activated in the presence of neutralizing serum immunoglobulin. Thus, we propose that memory relies on swIg(+) cells until they disappear and serum immunoglobulin falls to a low level, in which case memory resides with durable IgM(+) reserves.     

Susceptibility of the Mexican bean beetle <Emphasis Type="Italic">Epilachna varivestis</Emphasis> Mulsant (Coleoptera: Coccinellidae) to endemic isolates of <Emphasis Type="Italic">Beauveria bassiana</Emphasis> (Balsamo) Vuillemin (Hypocreales: Clavicipitaceae)

Entomopathogenic fungi represent excellent candidates for biological insecticides. Among the many entomopathogenic fungi, Beauveria bassiana (Balsamo) Vuillemin (Hypocreales: Clavicipitaceae) is one of the most promising species. Here, we report the results of infection studies performed using four B. bassiana native isolates (Bb37, Bb38, Bb40, and Bb45) compared with the commercial product Mycotrol^® (strain GHA) on adult Mexican bean beetle Epilachna varivestis Mulsant (Coleoptera: Coccinellidae), one of the most important pests of bean production in Mexico. First, single concentration (1 × 10⁸ conidia mL^?1) assays were carried out using all isolates applied using an immersion method. Examinations at 10 days after inoculation indicated that isolates Bb37, Bb38, and Bb40 significantly reduced adult survival, causing 60–75% mortality compared to the commercial strain GHA (33%) and control (29%). Second, using two selected isolates (Bb37 and Bb40), the mean lethal concentration values (LC₅₀) were estimated for third instar larvae and adult E. varivestis. The LC₅₀ values for Bb37 and Bb40 isolates decreased 5.26-fold and 3.19-fold, respectively, in third instars compared with adults. However, such difference for Bb40 isolate was not significant. Finally, an experiment, to compare the median survival time (MST) values between third instar and adult E. varivestis, was conducted using Bb37 and Bb40 at 1 × 10⁹ conidia mL^?1. MST values were significantly reduced against larvae (87 and 100 h) compared with adults (130 and 134 h) by Bb37 and Bb40, respectively. We conclude that native isolates of B. bassiana represent an important alternative for the control of E. varivestis. However, to demonstrate its effectiveness under field conditions, detailed studies are needed.     

Lower respiratory tract infections in cats: reaching beyond empirical therapy

PRACTICAL RELEVANCE: Lower respiratory tract infections (LRTIs) in cats can be due to bacteria, parasites, fungi and viruses. This review details the practical investigation of these infections and highlights specific therapy where possible. The aim is to avoid the all-too-frequent temptation in practice to treat cats with lower respiratory tract signs empirically for feline bronchial disease (FBD)/asthma. This is potentially hazardous as immunosuppressive therapy for FBD/asthma could exacerbate disease due to a LRTI. Empirical treatment of suspected LRTI is also difficult to recommend given the wide range of potential pathogens. CLINICAL CHALLENGES: Making a clinical ante-mortem diagnosis of LRTI in a cat can be challenging. Consistent historical, clinical, haematological and radiographic abnormalities are often lacking and findings may be non-specific. Astute clinical acumen, thorough investigation and high quality laboratory analysis are usually required for a diagnosis. Bronchoalveolar lavage, if feasible, and tests for lungworm should be routine in cats with lower respiratory tract signs. Lung fine needle aspiration may be useful in cases of diffuse or nodular pulmonary disease. Histopathology is rarely employed in ante-mortem investigations. EVIDENCE BASE: The authors have reviewed a substantial body of literature to provide information on many of the reported bacterial, parasitic, fungal and viral pathogens, including some that occur in Asia. Attention has been given to specific therapy for each pathogen, with evidence-based comments when there is a deviation from routine recommendations.