Sex differences in host resistance to Mycobacterium marinum infection in mice

Abstract

Sex differences were observed in host resistance to Mycobacterium marinum infection in mice. Males were found to be more susceptible than females in terms of mortality, incidence of gross skin lesions, and bacterial load in the lungs and spleen. The degree of sex differences varied from strain to strain of test mice, in the order C3H1/I1e, A/J, and BALB/c > DBA/2, B10.A, and C57BL/6, on the basis of survival time and multiplication of organisms in the visceral organs. Although this ordering corresponded to the susceptibilities of both male and female mice to the organisms, much greater strain dependency was seen in males than in females. Castration caused an increase in the host resistance of males, but this effect was substantially reversed by continuous testosterone treatment. Testosterone also increased the susceptibility of female mice to this infection. These findings imply that the male sex hormone is involved in the lowered anti-M. marinum resistance of males. Although athymic mice were more susceptible than euthymic mice, a substantial degree of sex difference was also observed in the T-cell-depleted animals, indicating that natural host resistance to this infection is sex dependent. Indeed, more efficient macrophage mobilization at the site of infection was seen in females than in males. Although female T-cell transplantation improved the lowered resistance of athymic mice, there was a sex difference in bacterial growth in the lungs. This implies that sex hormones affect T-cell functions. Sex differences in host resistance have been reported in mycobacterial infections, such as those due to Mycobacterium lepraemurium (6) and the M. avium complex (33), in mice. Males are more susceptible to these infections than are females; hence, participation of sex hormones in this phenomenon has been suggested. In humans, males predominate in the incidence of M. avium complex and M. kansasii infections (1, 21, 27, 34). Estrogens increase the resistance of host animals to infections such as those caused by Salmonella (20), Streptococcus (20), Pasteurella (20), and Trypanosoma (17) species. However, it has been reported that resistance to listerial (24, 25), staphylococcal (32), gonococcal (15), and chlamydial (26) infections is conversely reduced by the same sex hormone. In Leishmania major infection, orchidectomy causes increased resistance in male mice and administration of testosterone decreases anti-L. major resistance in female mice (18). We previously reported that sex differences in host resistance to M. avium complex infection in BALB/c mice are partly attributable to the antimicrobial activity of host macrophages (M@). Specifically, peritoneal M4) from female mice show more potent anti-M. avium complex activity than do M4 from male mice (33). However, detailed mechanisms of the sex differences in host resistance to mycobacterial infections still await elucidation. M. marinum is the causative agent of swimming pool granuloma or fish tank granuloma in humans, and a similar disease is produced in experimental an...

A comparison of cell mediators and serum cytokines transcript expression between male and female mice infected withMycobacterium aviumsubspeciesparatuberculosisand/or consuming probiotics

“…Group V includes genes important toward producing reactive oxygen species (ROS) and oxidative stress, but also mediators active during bacterial infection. cell-mediated immune responses vs. female mice (Yamamoto et al, 1991). Castrating male mice before infection showed similar rates of infectivity to females and female mice given testosterone were found to be more susceptible to M. marinum compared to controls females (Yamamoto et al, 1991).…”

“…cell-mediated immune responses vs. female mice (Yamamoto et al, 1991). Castrating male mice before infection showed similar rates of infectivity to females and female mice given testosterone were found to be more susceptible to M. marinum compared to controls females (Yamamoto et al, 1991). Although, these studies and our observations may be attributed to murine strain specificity, consistent observation of these trends distinct to each sex, combined with sex-specific microbial population densities, and across multiple modelssuggests that sex factors into immune response and to foreign microorganisms (Aziz, 2002;Marriott, 2006;Arnold, 2009;Gomez et al, 2012;Markle et al, 2013).…”

Effect of oestrogen onMycobacterium aviumcomplex pulmonary infection in mice

“…There have been some reports about the relation between sex and mycobacterial infections using experimental murine infection, such as those due to M. intracellulare [27], M. marinum [28] and M. leprae [29]. They all showed that females were more resistant to the infections than males.…”

Sexual dimorphism in lung function responses to acute influenza A infection

“…18 The few studies of sex differences in murine models of infectious respiratory disease generally investigate bacterial or mycobacterial (not viral) infection with results that vary depending on the pathogen; female C57BL ⁄ 6 mice are more susceptible to and show greater inflammatory responses to Pseudomonas aeruginosa infection than males, 3 yet male mice of various strains develop more severe lung lesions and greater mortality resulting from mycobacterial infection. 19,20 Thus, previous studies suggest that males may be more susceptible to infection because of their reduced ability to mount an appropriate inflammatory response compared with females. This lessened response may reduce cytokine-⁄ chemokine-related damage to the airways ⁄ parenchyma in males, which may be reflected in lessened responsiveness to bronchoconstrictive agents.…”