Home Sweet Home: Plasmodium vivax-Infected Reticulocytes—The Younger the Better?

After a century of constant failure to produce an in vitro culture of the most widespread human malaria parasite Plasmodium vivax, recent advances have highlighted the difficulties to provide this parasite with a healthy host cell to invade, develop, and multiply under in vitro conditions. The actual level of understanding of the heterogeneous populations of cells—framed under the name ‘reticulocytes’—and, importantly, their adequate in vitro progression from very immature reticulocytes to normocytes (mature erythrocytes) is far from complete. The volatility of its individual stability may suggest the reticulocyte as a delusory cell, particularly to be used for stable culture purposes. Yet, the recent relevance gained by a specific subset of highly immature reticulocytes has brought some hope. Very immature reticulocytes are characterized by a peculiar membrane harboring a plethora of molecules potentially involved in P. vivax invasion and by an intracellular complexity dynamically changing upon its quick maturation into normocytes. We analyze the potentialities offered by this youngest reticulocyte subsets as an ideal in vitro host cell for P. vivax.

Unexpected termite inquilines in nests of Constrictotermes cyphergaster (Silvestri, 1901) (Blattodea: Isoptera)

The heterospecific termite-termite cohabitation in a single termitarium, so called in-quilinism, is a common event whose basal mechanisms remain hypothetical. While some termite hosts have plenty of inquilines, others house only a few. Among these, Constrictotermes cyphergaster are frequently found cohabiting with a single obligate inquiline species but have been unknown to house any facultative inquilines. Here we present the first record of facultative inquilines (Embiratermes festivellus, Nasutitermes kemneri, Obitusitermes bacchanalis and Subulitermes) to this host, evidencing that this was unlikely to have happened fortuitously. In an attempt to pose hypotheses on the mechanisms behind such invasions, we explored likely connections between the settlement of obligate and facultative inquilines and nest wall’s physical traits. We found that nests bearing atypical external walls (moist, eroded, and partially covered by mosses) held higher richness of facultative inquilines than nests presenting walls void of such traits (χ2 = 8.3965, 1 df, n = 17, P = 0.0038). The presence of healthy host colonies in all nests, including the atypical ones, reinforces the hypothesis that the settlement of these facultative inquilines depends less on host colonies biotic status and more on abiotic features associated to the nest. In addition, the presence of obligate inquilines was not affected by the nest wall status (χ2 = 8.3965, 1 df, n = 17, P = 0.0038), implying that invasion by facultative and obligate inquilines in these nests would obey distinct restrictions. While warning that these hypotheses require further testing, we suggest that their understanding could shed light on the determinants of cohabitation not only in C. cyphergaster but in termites in general. cohabitation interspecific interaction nest invasion barriers

Kunkel Lecture: Fundamental immunodeficiency and its correction

“Fundamental immunodeficiency” is the inability of the encoded immune system to protect an otherwise healthy host from every infection that could threaten its life. In contrast to primary immunodeficiencies, fundamental immunodeficiency is not rare but nearly universal. It results not from variation in a given host gene but from the rate and extent of variation in the genes of other organisms. The remedy for fundamental immunodeficiency is “adopted immunity,” not to be confused with adaptive or adoptive immunity. Adopted immunity arises from four critical societal contributions to the survival of the human species: sanitation, nutrition, vaccines, and antimicrobial agents. Immunologists have a great deal to contribute to the development of vaccines and antimicrobial agents, but they have focused chiefly on vaccines, and vaccinology is thriving. In contrast, the effect of antimicrobial agents in adopted immunity, although fundamental, is fragile and failing. Immunologists can aid the development of sorely needed antimicrobial agents, and the study of antimicrobial agents can help immunologists discover targets and mechanisms of host immunity.

Lactobacillus rhamnosus RC007 intended for feed additive: immune-stimulatory properties and ameliorating effects on TNBS-induced colitis

Lactobacillus rhamnosus RC007 is a potential probiotic bacterium that can exert beneficial effects as supplement for animal feed, by improving the immune status in healthy host, and by providing therapeutic benefits to infected/inflamed animals. The aim of the present work was to evaluate in vivo the beneficial properties of L. rhamnosus RC007, intended for animal feed, when administered to healthy and trinitro-benzene-sulfonic-acid (TNBS) colitis induced BALB/c mice. The administration of L. rhamnosus RC007 to healthy mice during 10 days increased the phagocytic activity of peritoneal macrophages and the number of immunoglobulin A+ cells in the lamina proper of the small intestine. Significant increases of monocyte chemotactic protein 1, interleukin (IL)-10 and tumour necrosis factor alpha (TNF-α) concentrations, and in the ratio between anti- and pro-inflammatory cytokines (IL-10/TNF-α) were observed in intestinal fluids after administration of bacteria. In the inflammation model, less body weight loss, macroscopic and histological damages in the large intestine were accompanied by increased IL-10/TNF-α ratio in the intestinal fluids of mice from the L. rhamnosus-TNBS group when compared to the TNBS group. In a healthy host, the oral administration of L. rhamnosus RC007 kept the gut immune system stimulated allowing a faster response to noxious stimulus. Mice that received L. rhamnosus RC007 also decreased the severity of the intestinal inflammation.

Variation in Candida albicans EFG1 Expression Enables Host-Dependent Changes in Colonizing Fungal Populations

ABSTRACTTo understand differences in host-Candida albicansinteractions that occur during colonization of healthy or compromised hosts, production of phenotypic variants and colonization of healthy or immunodeficient mice byC. albicanswere studied. We showed that activity of the transcription factor Efg1p exhibited cell-to-cell variability and identified Efg1p as a major regulator of colonization. InC. albicanspopulations colonizing the murine gastrointestinal tract, average expression ofEFG1differed depending on the immune status of the host. We propose that cellular heterogeneity in Efg1p activity allows theC. albicanscolonizing population to differ depending on the immune status of the host, because selective pressure from a healthy host alters the composition of the population. These data are the first demonstration that differences in host immune status are associated with differences in gene expression in colonizingC. albicanscells. Altered gene expression in organisms colonizing immunocompromised hosts may begin the transition ofC. albicansfrom a commensal to a pathogen.IMPORTANCEIn healthy people, the fungusCandida albicanscolonizes the gastrointestinal tract and other sites without producing obvious pathology. In an immunocompromised patient, the organism can cause serious disease. The demonstration that the expression and activity of theC. albicanstranscription factor Efg1p differs during colonization of healthy or immunocompromised mice shows that the organism adjusts its physiology when colonizing different hosts. Further, the effects of a healthy host on a heterogeneousC. albicanspopulation containing cells with different levels of Efg1p activity show that selective pressure in the host can change the makeup of the population, allowing the population to respond to host immune status. The ability to sense host status may be key to the ability ofC. albicansto colonize as a harmless commensal in some hosts but become a deadly pathogen in others.