Induction of Non‐Specific Immunosuppression in Mice by Mycobacterial Infections and Its Relationship to Macrophage Activation

Abstract

The development of non-specific immunosuppression during the infection of different strains of mice with three mycobacterial species was evaluated by studying the immune response to a heterologous antigen (sheep red blood cells) and comparing it with the induction of non-specific resistance to a Listeria monocytogenes challenge. It was shown that early (at 15 days) immunosuppression developed in Mycobacterium avium-susceptible mouse strains infected with a high inoculum dose [2.5 x 10(8) colony forming units (CFU)] of virulent M. avium but not in resistant mice infected with a similar inoculum nor in susceptible mice infected by a smaller inoculum dose (2.5 x 10(6) CFU). In the latter case it developed only during the second month of infection and was of smaller magnitude. An inoculum of M. avium of attenuated virulence did not induce immunosuppression. M. lepraemurium induced a late immunosuppression, which occurred when extensive bacterial proliferation had already taken place. The non-pathogenic M. bovis BCG induced immunosuppression in C57BL/6 mice. The results do not establish a correlation between the development of generalized immunosuppression and susceptibility to infection. It could be seen that the early immunosuppression was observed in those situations where there was extensive macrophage activation as shown by the development of non-specific resistance to a listeria challenge. The late immunosuppression was observed when bacterial proliferation was extensive.

Mycobacteria-induced autoantibody production is associated with susceptibility to infection but not with host propensity to develop autoimmune disease

“…avium infection in two additional murine strains: C57B1/ 6-lpr/lpr mice that are both autoimmunity-prone and Myco. avium-susceptible animals [8], and also C.D2 mice that are both non-autoimmune and Myco. avium-resistant animals [9].…”

“…Previous investigations had also demonstrated that NZW and C57BI/6-lpr/lpr mice are susceptible (they carry the Bcgf allele of the Bcg gene) to Myco. avium infection, whereas NZB and C.D2 mice are resistant (bearing the Bcgr allele) to the same infectious agent [7][8][9][10].…”

Down‐Regulatory Effect of Mycobacterium leprae Cell Wall Lipids on Phagocytosis, Oxidative Respiratory Burst and Tumour Cell Killing by Mouse Bone Marrow Derived Macrophages

“…It has been reported in the literature that Mycobacteria antigens [15,34,35], and specifically ML antigens [5], inhibit superoxide production by macrophages. Our data clearly confirm these observations considering that ML or LE deeply suppressed O 2 -production by BMD macrophages.…”

“…The role of macrophages on the control of mycobacteria infection is still unclear despite the great efforts addressed to this issue [1,[3][4][5][6][7][8][9][10][15][16][17][18][19][20][21][22][23]. Since macrophages are the obligatory homing for pathogen mycobacteria in the tissues, we decided to investigate further the effects of dead M. leprae and its lipidic content on macrophage activation evaluating the phagocytic ability, superoxide production and tumour cell killing ability of these cells.…”

Generalized Immunological Decline during Long-Term Experimental Infection withMycobacterium avium

“…Measurement of the production of IFN-␥ from in vitro-cultured lung cells as described above for spleens was ruled out, because they produced inordinately low titers of IFN-␥ (data not shown). Because cells recovered from the lung comprised over 70% macrophages and other large cells, it is likely that this was due to either a relative shortage of T cells in cultures or suppression by products of activated macrophages (1,13). Lungs were removed from groups of three mice at different stages of infection and subjected to enzymatic digestion to generate single-cell suspensions (14).…”