Understanding the ecology of drug-resistant pathogens is essential for devising rational programs to preserve the effective lifespan of antimicrobial agents and to abrogate epidemics of drug-resistant organisms. Mathematical models predict that strain fitness is an important determinant of multidrug-resistant Mycobacterium tuberculosis transmission, but the effects of strain diversity have been largely overlooked. Here we compared the impact of resistance mutations on the transmission of isoniazid-resistant M. tuberculosis in San Francisco during a 9-y period. Strains with a KatG S315T or inhA promoter mutation were more likely to spread than strains with other mutations. The impact of these mutations on the transmission of isoniazid-resistant strains was comparable to the effect of other clinical determinants of transmission. Associations were apparent between specific drug resistance mutations and the main M. tuberculosis lineages. Our results show that in addition to host and environmental factors, strain genetic diversity can influence the transmission dynamics of drug-resistant bacteria. Resistance to antibiotics is an increasing global public health problem. Multidrug-resistant tuberculosis is threatening the control of this deadly infectious disease in many parts of the world. Studies to identify the factors that lead to the emergence and subsequent spread of drug-resistant organisms have clearly shown that patient adherence to a 6 mo course of treatment is very important to prevent the development of drug-resistant tuberculosis. However, little is known about how bacterial genetics might influence the spread of drug-resistant strains. This study showed that among the strains in San Francisco with resistance to isoniazid, one of the main anti-tuberculosis drugs, only certain strains were transmitted effectively. The transmission of specific isoniazid-resistant strains depended on the type of genetic mutation leading to resistance. Also, isoniazid-resistant strains coming from different parts of the world were associated with different resistance mutations. This study's results show that the spread of drug resistance is due to the strain of tuberculosis as well as the environment and characteristics of the patient, and may partially explain why some areas of the world have worse drug resistance problems than others.

Mast cells are unique tissue-resident immune cells that secrete a diverse array of biologically active compounds that can stimulate, modulate, or suppress the immune response. Although mounting evidence supports that mast cells are consistently infiltrating tumors, their role as either a driving or an opposite force for cancer progression is still controversial. Particularly, in breast cancer, their function is still under discussion. While some studies have shown a protective role, recent evidence indicates that mast cells enhance blood and lymphatic vessel formation. Interestingly, one of the most important components of the mast cell cargo, the serine protease tryptase, is a potent angiogenic factor, and elevated serum tryptase levels correlate with bad prognosis in breast cancer patients. Likewise, histamine is known to induce tumor cell proliferation and tumor growth. In agreement, mast cell depletion reduces the size of mammary tumors and metastasis in murine models that spontaneously develop breast cancer. In this review, we will discuss the evidence supporting protumoral and antitumoral roles of mast cells, emphasizing recent findings placing mast cells as important drivers of tumor progression, as well as the potential use of these cells or their mediators as therapeutic targets.

Mast cells (MC) are abundant in the lung and other peripheral tissue, where they participate in inflammatory processes against bacterial infections. Like other effector cells of the innate immune system, MC interact directly with a wide variety of infectious agents. This interaction results in MC activation and inflammatory mediator release. We demonstrated that MC interact with Mycobacterium tuberculosis, triggering the release of several prestored reagents, such as histamine and β-hexosaminidase, and de novo synthesized cytokines, such as TNF-α and IL-6. A number of M. tuberculosis Ags, ESAT-6, MTSA-10, and MPT-63, have been implicated in MC activation and mediator release. A MC plasmalemmal protein, CD48, was implicated in interactions with mycobacteria because CD48 appeared to aggregate in the MC membrane at sites of bacterial binding and because Abs to CD48 inhibited the MC histamine response to mycobacteria. Cumulatively, these findings suggest that MC, even in the absence of opsonins, can directly recognize M. tuberculosis and its Ags and have the potential to play an active role in mediating the host’s innate response to M. tuberculosis infection.

Sex hormones play an important role as modulators of the immune system. A growing body of evidence shows reciprocal relationship between sex steroids and the immune system. Since the innate immune response determines the type of adaptive immune response, hormonal effects on the innate immune response may affect subsequent adaptive immunity. The sex steroids estrogens, progesterone and testosterone regulate growth, differentiation, survival and function of many cell types involved in homeostasis and immunity. The presence of sex steroid receptors on immune cells indicates that sex steroids may exert their biological effects by binding to these receptors. Sex steroids and immunity are closely connected, and their mutual regulation is involved in the maintenance of immune balance. Understanding the mechanisms of action of sex steroids on immune cells is important for further progress in the development of novel therapies for chronic diseases associated to immune dysregulation. This review describes the effects of sex steroids on the different immune system cells, and the possible implications of these effects on the incidence of many diseases